HX00019151 Qlolumbia ItttuFrBttg t« tl|? Olitu of ^m 1 flrk Utfnmt^ Hibrarg ANESTHESIA Digitized by the Internet Archive in 2010 with funding from Open Knowledge Commons http://www.archive.org/details/anesthesiaOOgwat ANESTHESIA BY JAMES TAYLOE GWATHMEY, M.D. FIRST PRESIDENT OF AMERICAN ASSOCIATION OF ANESTHETISTS, ANESTHETIST TO THE NEW YORK SKIN AND CANCER, ST. VINCENT, RED CROSS AND COLCMBIA HOSPITALS, AND ST. BARTHOLOMEW'S CLINIC, MEMBER OF AMERICAN MEDICAL ASSOCIATION AND THE NEW YORK ACADEMY OF MEDICINE IN COLLABORATION WITH CHARLES BASKERVILLE, Ph.D., F.C.S. PROFESSOR OF CHEMISTRY IN THE COLLEGE OF THE CITY OF NEW YORK, MEMBER AMERICAN AND GERMAN CHEMICAL SOCIETIES, ELECTRO-CHEMICAL SOCIETY, INSTITUTE OF CHEMICAL ENGINEERS, AMERICAN ASSOCIATION OF ANESTHETISTS, NEW YORK AND WASHINGTON ACADEMIES OF SCIENCE, ETC. WITH TWO HUNDRED AND EIGHTY-THREE ILLUSTRATIONS IN THE TEXT NEW YORK AND LONDON D. APPLETON AND COMPANY 1914 COPTRIGHT, 1914, BY D. APPLETON AND COMPANY s^..M; B /^/& ■■ / / Printed in the United States of America * t: C5> '^Even as a surgeon minding oft to cut Some careless limb, before in use he puts His violent engines in the victim's member, Bringeth his patient in a senseless slumber; And griefless then, guided by use and art, To save the whole, saws off the infested part." — DUBARTAS, 1592 A. D. LIST OF CONTRIBUTORS WILLIAM SEAMAN BAINBRIDGE, A.M., Sc.D., M.D. Professor of Surgery, N. Y, Polyclinic Medical School and Hospital; Sur- geon, N. Y. Skin and Cancer Hospital; Attending Surgeon, N. Y. City Children's Hospitals and Schools; Consult- ing Surgeon, Manhattan State Hospital, Ward's Island, Etc. JOHN W. H. CRIM, L.L, LL.B. Former Assistant United States Attorney; Former Special Assistant At- torney-General of the United States. CHARLES A. ELSE ERG, A.B., M.D. Professor of Clinical Surgery, University and Bellevue Hospital Medical College, New York; Attending Surgeon, Mount Sinai Hos- pital and New York Neurological Institute HORACE W. FRINK, M.D. W. D. GATCH, A.B., M.D. Professor of Surgery, Indiana University School of Medicine, Indianapolis, Ind. JAMES F. MITCHELL, A.B., M.D. Surgeon to Providence Hospital HERRMANN PRINZ, M.D., D.D.S. Professor of Dental Materia Medica, Pharmacology and Therapeutics, Thomas W. Evans Museum and Dental Institute, School of Dentistry, University of Pennsylvania, Philadelphia LOUISE G. ROBINOVITCH, B.esL., M.D. (Paris) Member, New York Academy of Medicine; Member, American Medical Association; Foreign Associate Member, Medico- Psychological Society, Paris WALTER S. SUTTON, A.B., A.M., M.D., F.A.C.S. Associate Professor of Surgerj^, University of Kansas School of Medicine, Attending Surgeon, Bell Memorial Hospital, Kansas City, Mo. JAMES J. WALSH, M.D., Ph.D., LL.D., K. St. G. Formerly Dean and Professor of Nervous Diseases, Fordham University School of Medicine, New York City PREFACE The administration of anesthetics, along with practically every other phase of medicine and surgery, is undergoing a steady evolution. The development in the application of anesthetics has been most marked within recent years, so that any given anesthetic or method which is considered the best to-day may be entirely replaced by a safer and a bet- ter to-morrow. Even to-day there is not a little divergence of opinion as to which is the best method. No longer are the leaders- in medicine and surgery satisfied with a form of anesthesia which simply renders the afflicted one insensible to pain during an operation, and which allows the surgeon to work with great freedom and confidence, but they insist j^urther, and rightly, upon maintaining the patient's vitality, reducing the effect of shock as much as possible, and having the patient as com- fortable as may be during recovery and convalescence. "Every hospital, certainly every large hospital, should have as a regu- lar member of its staff an attending anesthetist, as is the case in some, whose authority in his special department should be as complete as is that of the attending physician or surgeon in their fields. This arrange- ment will be particularly important during the next few years when the older methods of anesthesia — chloroform, ether, cocain, etc., — will be com- peting with, and greatly modified by, newer procedures, e. g., nitrous oxid, intratracheal insufflation, spinal anesthesia, intravenous anesthesia, intra-arterial injection of novocain by the methods of Bier and Eamshoff, measures for the prevention and relief of acapnia, the prevention of pain associations, etc." * The dignity of this special field in medicine can be greatly enhanced and its progress equally advanced by such organizations as the New York and American Societies of Anesthetists, wherein the theories and prac- tice are fully presented and discussed with the liveliest interest and general profit. * From the Report of the Committee on Anesthesia, American Medical Associa- tion, June, 1912. X PREFACE The main purposes of this book are : (1) To give in a practical and utilizable form the essentials of the subject of the administration of anesthetics; (2) To save the busy medical practitioner or student the labor of weeding out from the voluminous literature upon the subject the facts which he must constantly bear in mind in the successful practice of this important branch of medicine ; (3) To emphasize, wherever possible, the thought that "to bring a living being to that borderland in which life in many respects so simu- lates death should at no time be a fool's occupation" ; and (4) While primarily intended as a work for the active practitioner and student, to suggest many lines for further research. The authors will be grateful for suggestions, and especially for ac- counts of unusual experiences met with in practice. Due consideration has been given to the historical development of anesthesia, but emphasis has been laid upon modern American practice without neglecting European procedures. This has been accomplished by happily securing the cooperation of successful investigators — to whom sin- cere thanks are here extended, and whose names appear at the heads of those chapters prepared by them — within the various fields of the sub- ject. Ample space has, therefore, been given to methods of administra- tion which are as yet in the experimental stage, although dominant prom- inence has gone to those methods whose utility has become established. A list of anesthetics with valuable data and references (Chapter XX) is presented complete, as far as we are aware, for the first time. It is hoped that the contents of this chapter may prove of value not only to the profession of medicine, but to the professions of dentistry, pharmacy, and chemistry as well, for there the investigator may possibly find a drug more nearly ideal for his purposes than any now in general use for ob- tunding sensation or inducing unconsciousness. As modern medicine now more generally recognizes the importance of a knowledge of chemistry in all its branches, that phase of the sub- ject has been quite fully developed, not only along the lines of original purity of the drug used, the conditions favorable to its preservation in its highest purity, but its . course within the body, resulting either in the destruction of the drug or its elimination from the body. To some it might have been desirable to indicate from whom certain instruments could be obtained and to specify the quality of drugs sup- PREFACE xi plied by the different manufacturers, but for obvious reasons that could not be. As for the latter, the absolute purity of the drug administered cannot be too strongly emphasized. The standards of purity given in the text are those determined after prolonged and most painstaking in- vestigations. These standards of purity should be insisted upon by the physician. It is quite out of the question to have every sample to be used examined by an expert chemist — and only an expert chemist should pass upon the quality of an anesthetic — but occasional chemical examinations may be made, and, knowing the quality of the drug as supplied on the market, one must then place reliance upon the reputation of the firm supplying the drug. We have found the reputable houses anxious to pro- vide drugs of the highest purity, but unfortunately close chemical super- vision does not always obtain, and impure products do get upon the mar- ket through carelessness of workmen or failure to provide against de- terioration of the drug, even though it leave the manufacturer of a proper grade. James Tayloe Gwathmey. Charles Baskerville. New York City. CONTENTS CHAPTER I THE HISTORY OF ANESTHESIA PAGE Introductory Remarks : Ancient Histoiy ; Beginning- of the Christian Era; Asiatic Sources; Middle Ages; Hypnotism; Real Beginnings of SurgicaL Anesthesia ; Discovery of Ether Anesthesia; The Dis- covery of Nitrons Oxid for Surgical Anesthesia .... 1-11 Ether: Morton; Eirst Public Demonstration; Letheon; Anesthesia in England 11-19 Chloroform : Theological Opposition to the Use of Anesthetics ; The Early Use of Chloroform in Midwifery; Some Physicians Believe in Pain; Prejudice Developed against Chloroform; Scientific Ad- ministration of Ether and Chloroform; Efforts to Overcome Ob- jections to Chlorofoiin by Use of Substitutes and Improved In- halers; A.C.E. Mixture; Substitutes; First Vapor Inhaler; Nitrous Oxid More Generally Appreciated; Nitrous Oxid and Oxygen; Discarding Chloroform for Ether; Improved Methods for Administering Ether; Warmed Ether Vapor; Chloroform Condemned; Medication before Anesthesia; The Use of Chloro- form Accompanied with Danger; Chloroform and Oxygen; Com- binations and Sequences in Anesthesia; Ethyl Chlorid; Im- portance of Trained Anesthetists 20-27 Bibliography . • • 27-29 CHAPTER II general physiology of inhalation anesthesia Introductory Remarks : Definition of Terms ; Chief Anesthetic Agents 30-32 Theories of the Action of General Anesthetics: Spencer's Theory; Binz's Theory; Bernard's Theory; Dubois' Theoi-y; Schleich's Theory; Mliller's Theory; Meyer-Overton Theory; Wright's Theoi-y; Traube's Theoi-y; Mathews-Brown Theory; Moore-Roaf Theory; Gill's Theory; Hober's Theory; Baglioni's Theory; Reicher's Theory; Gros's Conclusions; Biirker's Theory; Verworn's Theory; Conclusions of Lillie; Conclusions . . 32-56 ij"- xiv CONTENTS PAGE Effects of General Anesthetics upon Various Parts of the Organism: The Respiratory System; The Circulatory System; The Muscular System; The Glandular System; The Nervous System 56-62 Factors Which May Be Said to Modify the Physiology of Anesthesia as Ordinarii;Y Induced: Warming the Agent; Experiments on Warming Ether ; Effects of Moisture ; Combining Oxygen with the Agent ; The Influence upon Anesthesia of Oxy- gen Intra-abdominally Administered; Preceding the Administra- tion with Oil of Bitter Orange Peel; Utilizing Carbon Dioxid 62-99 CHAPTER III THE USE OF REBREATHING IN THE ADMINISTRATION OF ANESTHETICS W. B. Gatch, M.D. Ether: Effect of Ether Vapor on Respiratory Passages; Compari- son of Toxic Effects Following Use of Open and Closed Methods ; Effects of Over-Concentration of Ether Vapor . . . 100-103 ITROUS OxiD, Alone and Combined with Ether: Method of Administration; Basis of Technique; Practical Advice; Main- tenance of Ether Balance; Elimination of Ether from the Sys- tem; Effect of Morphin on Ether Elimination; Clinical Results; Long Operations; Fatalities; Cardiac Cases; Hypercapnia; Acapnia; Ether and Acapnia; Other Advantages of Rebreathing; Post- Anesthetic Nausea; Post- Anesthetic Abdominal Distention; Post- Anesthetic Lung Complications; Method Demands Experi- ence 103-115 Chloroform and Ethyl Chlorid: Suggested Investigations; Dan- gers; Advantages 115-116 CHAPTER IV nitrous oxid / History: Early Use in Dentistry; Nitrous Oxid Administered with Oxygen; Physical Properties; Chemical Properties; Impurities of Nitrous Oxid; Standard of Purity 118-123 Special Physiology: The Hyper-Oxygenation Theory; The Deoxy- genation or Asphyxiation Theory; The Theory of the Specific Action of Nitrous Oxid upon the Brain Cells; Effects upon the Respiratory System ; Effects upon the Circulatory System ; Effects upon the Nervous System; Effects upon the Muscular System; Effects upon the Glandular System and Other Structures ; Causes of Death; Stages of Anesthesia; Elimination; After-effects 123-135 CONTENTS XV PAGB Comparison with Other Agents 135 Indications and Contraindications 135 Administration : Heating- the Gas ; Essential Features of Any Satisfactory Apparatus; Apparatus for Administering Nitrous Oxid Alone or With Air; Dangers of Administration of Nitrous Oxid Alone; Recognition of Asphyxial Symptoms; Administra- tion of Nitrous Oxid Alone ; Administration to Asphyxiation With and Without Valves; Use of Expiratory Valve Alone; Adminis- tration Without Valves; Precautions When Administered Alone; Administration of Nitrous Oxid With Air in Unknown Quanti- ties; Administration of Nitrous Oxid With Definite Amounts of Air; Nitrous Oxid as a Sequence to Ether; Nitrous Oxid With Air; Technique of Ether-Nitrous Oxid (Air) Sequences; Tech- nique With A.C.E. ; Advantages of Ether (or Chlorof orm-Ether) - Nitrous Oxid Sequence; The Advantages of Administration of Nitrous Oxid With Oxygen; Superiority of Oxygen Over Air; The Administration of Nitrous Oxid With Indefinite Quantities of Oxygen; Gatch's Method of Administration; Davis's Method; Methods of Administration with Definite Quantities of Nitrous Oxid and Oxygen; Gwathmey's Method; Teter's Method; Tech- nique to be Followed in Administering Nitrous Oxid and Oxygen With the Teter Apparatus and the Teter Nasal Inhaler; Nitrous Oxid Oxygen Endopharyngeally ; Boothby and Cotton Apparatus ; The Gwathmey-Woolsey Nitrous Oxid-Oxygen Apparatus . 136-175 CHAPTER V ETHER History of the Use of Ether as Anesthetic .... 176-178 Chemistry: The Term Ether; Properties of Ether; Anesthetic Ether; Precautions in Handling Ether; Sources of Impurities in Ether ; Standards of Purity With Which Anesthetic Ether Should Comply; Role of Alcohol in Ether; Peroxids; Aldehyd; Physio- logical Action of the Impurities and Administration Means to Avoid Them ' . . 178-184 Special Physiology: Effects Upon Respiratory System; Effects Upon Circulatory System ; Effects Upon Ners'ous System ; Effects Upon Muscular System; Effects Upon Glandular System and Other Structures; Causes of Death from the Administration of Ether; Stages of Ether Anesthesia; Elimination; After- effects 184-199 Administration of Ether: The Open or Drop Methods; The Mask; Ethyl Chlorid-Ether Sequence by the Drop Method; The Ethyl Chlorid-Ether-Chlorofoi-m Sequence; The Ethyl Chlorid- Ether Sequence by the Closed Method; Chloroform-Ether Se- quence; Anesthol-Ether Sequence by the Drop Method; The xvi CONTENTS PAGE Elhor Ransch; Tlie Semi-Closed Method; Towel and Paper Cones; The Handkerchief Method; The Closed Method; The Nitrous Oxid-Ether Sequence; Technique of the Nitrous Oxid-Ether Se- quence; Nitrous Oxid-Ether-Chloroform Sequence; The Vapor Method of Anesthesia; Warmed Ether Vapor . . . 199-231 Vapor: The Open Method; Endopharyngeal Anesthesia; Oxygen- Ether Administration; Concentration of Ether Vapor; The Closed Method ; Amount of the Anesthetic Used ; Care of the Apparatus ; Hints; Advantages; Treatment of Accidents .... 231-247 Indications and Contraindications of Ether: Indications; Con- traindications .......... 247-249 CHAPTER VI ETHYL CHLORID ■ V^HEMiSTRY : Chemical History ; Histoiy of Its Use as an Anesthetic ; Uses; Prepai'ation ; Properties; Storage and Containers; Impur- ities Which May Develop in Ethyl Chloiid; Detection of Im- purities in Ethyl Chlorid 250-258 Physiology : Effects upon Respiratory System ; Effects upon Cii'cula- tory System ; Effects Upon the Nervous System ; Effects Upon the Muscular System; Effects Upon the Glandular System; Causes of Death Under Ethyl Chlorid Anesthesia; Stages of Anesthesia; Elimination; After- Effects; Comparison With Other Anesthetic Agents 258-267 Indications and Contraindications 267-269 Administration : Experimental Data ; Methods of Administration ; Open Method ; Semi-Closed Method ; Closed Method ; Combi- nations and Sequences . . . . . . . . • 269-279 Bibliography 279-280 CHAPTER VII chloroform Chemistry: History; History of Its Use as an Anesthetic; Prop- erties; Uses; Preparation of Chloroform; Impurities Liable to Be Present in Chloroform ; Stability of Chloroform ; Decomposi- tion of Pure Chloroform; Role of Alcohol in Anesthetic Chloro- form; Character of Containers; Stoppers for the Containers; The Changes Which Anesthetic Chloroform Undergoes When a CuiTent of Oxygen is Conducted Through It; The Decomposition of Chloroform Vapor Upon Exposure to Gas Light, Etc., Dur- ing Administration ; Effect of Agitation Upon Anesthetic Chloro- foi-m; Standards of Purity for Anesthetic Chloroform , 281-296 CONTENTS xvii PAGE Special Physiology: Effects Upon the Respiratory System; Effects Upon the Circulatory System ; Effects Upon the Nei"vous System ; Effects Upon the Muscular System ; Effects Upon the Glandular System and Other Structures; (^auses of Death from tlie Ad- ministration of Cliloroform ; Stages of Anesthesia; Elimina- tion 297-310 Indications and Contraindications: Indications; Contraindica- tions; After-Effects; Comparison with Other Agents . . 310-311 Administration of Chloroform: Drop Method; Other Methods of Administration ; The Roth-Drager Oxygen and Chloroform Ap- paratus; Vernon Hareourt's Inhaler; Junker Apparatus; Braun's Inhaler; Gwathmey Three-Bottle Vapor Inhaler . 311-324 CHAPTER VIII THE selection OF THE ANESTHETIC AND TECHNIQUE FOR SPECIAL OPERATIONS Conditions Affecting Selection: Inhalation Anesthetics; Safest Anesthetic; Chloroform with Oxygen; Value of Combinations and Sequence in Anesthetics; Safest Sequences . . 324—326 Rules to Be Obeyed in Selecting the Anesthetic : Age ; Heart Disease; Pulmonary Tuberculosis; Obese Patients; Thin Sub- jects; Athletes; Alcoholics, and Other Drug Habitues; Diseases of the Lungs; Kidney Diseases; Cancer; Nervous Patients; Epi- leptics; Insane Patients; Status Lymphaticus _ . . . 326-337 Special Operations: Short Operations; Nitrous Oxid; Ethyl Chlorid; Chloroform and Ether; The Mastoid; The Upper Res- piratory Tract; Excision of the Tongue; Cleft Palate; Sub- mucous Operations; Adenoid and Tonsil Cases; Tracheotomy; Goiter (Angina, Ludovici, Exophthalmos — Graves' Disease) ; Amputations; Operations Upon Fingers and Toes; Circumcision; Rectal Cases; Obstetric Cases; Curettage; Genito-urinary Opera- tions; Laparotomy; Gastro-enterostomy and Similar Operations; Peritonitis or Intestinal Obstruction . . . . . . 357 Conclusions 357 Bibliography 357-358 CHAPTER IX treatment before, during, AND AFTER ANESTHESIA Duties of the Anesthetist in Addition to Giving the Anes- thetic 361-362 The Anesthetist^s Kit : Anesthetist's . Motto ; Mouth Gag ; Con- tents of Kit; Emergency Treatment to Insure Breathing 362-363 xviii CONTENTS PAGE The Management of Ordinary Cases: Preliminary Treatment; Treatment During Anesthesia; After-treatment . . . 364-379 Management of Difficult and Unusual Cases: Respiratoi-y ; Muscular; Nervous; Idiosyncratic; Shock; Post-Anesthetic Toxemia 379^15 CHAPTER X anesthesia by intratracheal insufflation Definition 416 History 416 The Apparatus for Intratracheal Anesthesia in the Human Being: Apparatus No. I; Apparatus No. II; The Catheter or Tube to Be Used; The Introduction of the Tube . . . 419^29 The Course of the Anesthesia 429-430 Errors Which May Occur in Technique: Accidents and How They May Be Avoided 430 Indications for Intratracheal Anesthesia 431 Bibliography 432 CHAPTER XI Part I ANESTHESIA BY COLONIC ABSORPTION OF ETHER Walter S. Sutton, A.B., A.M., M.D., E.A.C.S. History 433-439 The Physiology of Colonic Anesthesia 439-441 Development of the Method 441^4i4 Sutton's Apparatus: The Generator 444-449 The Afferent and Efferent Tube Systems .... 449-450 Technique op Method: Preparation of Patient; The Administra- tion; After-treatment 450-453 Discussion of Cases 453^57 Conclusions: Indications; Contraindications; Advantages; Disad- vantages 457-458 Part II oil-ether colonic anesthesia History 458 Animal Experiments 458-460 Remarks on the Method 460 CONTENTS xix PAGE Prepaeation of the Patient: Preliminary Medication . . 460-461 Administration 461 Control of the Anesthesia 461-462 Physiology 462 Illustrative Cases 463 CHAPTER XII sequestration method of anesthesia History 467 Technique 468 Indications: Brain Surgery; Goiter 469 Contraindications 469 Modifications in the Method : Advantages ; Disadvantages ; Seques- tration with, the Upright Position 470-475 CHAPTER XIII Part I local anesthesia James F. Mitchell^ M.D. History: Adrenalin; Cocain Substitutes; Arterial Injection; Ex- planation of Poisonous Action of Cocain; Preparation of Solu- tions; Sterilizing the Solutions; Novocain; Urea and Quinin Hy- drochlorid; Syringes; Indications and Scope of Local Anes- thesia; Local Versus General Anesthesia; Mortality; General Preparation and Technique; Details as to Comfort of Patient; After-treatment; Healing; Combination of Local and General Anesthesia 476-488 Methods : Surface Application ; Infiltration ; The Regional Method ; Venous Anesthesia; Arterial Anesthesia .... 488-493 Special Application: Skin; Head and Neck; Face; Ear; Nose and Accessory Sinuses, Tonsils; Eye; Neck; Tracheotomy; Larsnax; Thyroid; Thorax and Breast; The Extremities; Genito-urinaiy ; System; Circumcision; Rectum; Gynecology; Abdomen; Inguinal Hernia 493-523 Part II intravenous anesthesia Physiology 524 Technique 524-532 Mixed Forms op Anesthesia 532-533 XX CONTENTS PAGE Blood Changes • 533 Urinary Examination . • • 534 CHAPTER XIV LOCAL ANESTHESIA AS APPLIED IN DENTISTRY Herrmann Prinz_, M.D., D.D.S. History • • 535-536 The Hypodermic Method 536 Cold 537 Mode of Application op Ethyl Chlorid 537 Cocain: Preparation of Cocain Solutions; Sterilization of Solutions; Substitutes Proposed for Cocain; The Hypodermic Armamenta- rium 538-543 Technique of Injection : The Subperiosteal Injection ; Peridental Anesthesia; Intra-osseus Injection; Perineural Injection; The Injection into the Pulp; Methods of Anesthetizing the Pulp 543-553 CHAPTER XV spinal analgesia and spinal anesthesia Introduction 554-555 History: Discoveiy of and Experimentation with Cocain; Experi- mentation with Cocain from the Neurological Point of View with Regard to Its Analgesic Effects Upon the Sensory Nerves, Including the Spinal Cord; Application of the Analgesic Effects of Cocain Upon the Cord to Surgical Operations Below the Dia- phragm; Extension of the Surgical Application of Spinal Anal- gesia to Parts of the Body Above the Diaphragm ; Experimenta- tion with Other Agents ' . . 555-563 Anatomical and Physiological Considerations: Origin; Vol- ume; Specific Gravity; Movements; Pressure; Diffusion . 563-572 Course, Extent, and Duration of Analgesia: Course; Extent; Duration . 572-577 Accompanying Phenomena: Subjective; Objective . . . 577-582 Post-operative Phenomena 582-586 Indications and Contraindications 586-594 Advantages and Disadvantages: Advantages; Disadvantages 594-596 Deaths 596-599 Analgesic Agents : Cocain ; Tropoeocain ; Stovain ; Novocain 599-604 Sterilization of the Analgesic Agent 604-605 Sites of Injection 605-612 The Patient: Preliminaiy Preparation of Patient; Position of Patient 612-614 CONTENTS xxi PAGK Apparatus and Materials . . . • , • • • • 014-617 Technique of Injection - 017-623 Additional Illustrative Case Reports . . . • • 623-626 Conclusions 627 CHAPTER XVI ELECTRIC ANALGESIA^ SLEEP^ AND RESUSCITATION Louise G. Robinovitch, B. esL., M.D. (Paris) History : Electric Source and Technique ; Application in Man ; Con- traindications ; Electric Analgesia and Sleep in Wireless Circuits; Conclusions 628-63C Electric Analgesia and Electric Resuscitation After Heart Failure Under Chloroform or Electrocution: Exclusion of the Head; Kind of Current Used; Procedure; Limitations; Ap- plication in Accidental Electrocution; Application in Surgery; Clinical Applications 637-643 CHAPTER XVII Part I MENTAL influence IN ANESTHESIA James J. Walsh, M.D. Hypnotism: Anesthesia in Hypnotic States; Chemical Anesthetics and Hypnotism; Advantages of Hypnotism in Anesthesia; Hyp- notism and Childbirth; Hypnotism in Minor Operations; Ad- vantages of Hypnotism ; Charlatanism and Hypnotism . . 644—649 Suggestion: Suggestion Instead of Hypnotism; Psychic Influences and Surgical Anesthesia ; Local Anesthesia and Mental Influence ; Mental Influence as a Valuable Auxiliary; Deep Breathing and Concentration of Mind; Preliminary Medication and Mental Influence ■. . 649-653 Part II HYPNOSIS IN anesthesia H. W. Frink, M.D. Hypnosis: The Different Degrees of Hypnosis and Some of the Phenomena Accompanying Them ; Factors Which Influence Sug- gestibility ; The Attitude of the Hypnotist ; Methods of Inducing the State of Hypnosis; The Induction of Anesthesia . 653-665 CONTENTS CHAPTER XVIII THERAPEUTIC USES OF INHALATION ANESTHETICS PAGE Anesthetic Treatment for Special Conditions: In Renal and Biliary Colic; In Cases of Acute Pain or Shock; In the Passage of Renal or Biliary Calculi; Extreme Irritability of the Central Nervous System; Convulsions of Infancy and Childhood; Puer- peral Eclampsia; In Anemic Convulsions; Convulsions and Seiz- ures Depending Upon Poisoning, and Cerebral Diseases; Use in Diagnosis; Insomnia or Extreme Restlessness; Acute Mania; Some Miscellaneous Applications of Ethyl Chlorid . . 666-671 Other Uses of Agents Employed in the Administration of An- esthetics : Ether in the Treatment of Infections ; Ether Irriga- tion of the Abdomen 671-674 CHAPTER XIX the medico-legal status of the anesthetist John W. H. Crim Introduction: Police power; The Medical Profession Established; Contest Between the Schools of Medicine; The Status of the Physician 675-680 The Physician's Liability: Ethical Liability of the Physician; The Civil Liability of the Physician; Malpractice; Liability of the Specialist; The Criminal Liability of the Physician; Gross Ignorance or Negligence ; Statutory Liability .... 680-687 CHAPTER XX A LIST OF anesthetics Including General Anesthetics^ Local Anesthetics^ and Anes- thetic Mixtures^ Both Past and Present, with Synonyms 688-840 CHAPTER XXI statistics Introduction 841-843 Collateral Information: Local Anesthesia; Nitrous Oxid Alone or with Air; Nitrous Oxid with Oxygen; Anesthol-Ether Se- CONTENTS xxiii PAGE quence; Chloroform-Ether Sequence; Nitrous Oxid-Ether Se- quence; Anesthol; Ether, Drop or Vapor; Ethyl Chlorid- Ether Sequence; Ethyl Chlorid; Chloroform-Oxygen; Chloroform, Drop or Vapor; Intratracheal Anesthesia; Oil of Bitter Orange Peel- Ether Sequence, Comparison of Amerisan Statistics for 1905-1911 with Those for 1892; Comparison of American with European Statistics; American Statistics, 1905-1912, Inc. . . . 844-856 Conclusions 857 APPENDIX I ETHTIi ETHER History of Ethyl Ether 858-860 Manufacture of Ether: Ether from "Methylated" Alcohol; Ether from Ethylene; Theories of Etherification .... 860-863 Purity of Ether: The Commercial Purification of Ether; Verified Tests for Proving Purity of Anesthetic Ether; Role of Water in Anesthetic Ether; Explanation of Changes Liable to Occur in Ether Improperly Stored; The Purification of Ether Remnants with the View of Removing Aldehyd in Particular; Acidity of Ether and Effect Thereon of the Container; Physiological Con- sideration in Reference to Small Amounts of Impurities ; The De- grees of Purity of American Ethyl Ethers Used for Anesthesia 864r-S70 APPENDIX II chloroform: History of Chloroform . . 871-873 Preparation of Chloroform : From Ethyl Alcohol ; From "Methyl- ated Spirit"; From Acetone; From Methane; From Carbon Tetrachlorid 873-875 . Varieties of Chloroform of European Make : Chloral Chloroform ; Chloroform Pictet; Chloroform Anschiitz ..... 876 Purification of Chloroform 877-883 The Decomposition of Chloroform: The Changes Which Chloro- form Undergoes Upon Exposure to Air .... 883-888 Verified Tests for Purity of Anesthetic Chloroform: Odor; Residue; Specific Gravity; Organic Impurities; Acetone; Aeetal- dehyd; Acidity; The Decomposition Products of Anesthetic Chloroform 889-890 Degrees of Purity of American Chloroforms .... 891 CONTENTS APPENDIX III OXYGEN PAGE History of Oxygen 893 Methods op Manufacturing Medical Oxygen .... 893 Impurities That May Be Present in Oxygen , . . " . 894 Purity op Commercial Medicinal Oxygen 895 Standards of Purity That Should Be Required for Oxygen to Be Used in Medicine 895 Index , , » . 897 LIST OF ILLUSTRATIONS FIG. PAGE 1. Henry Hill Hickman 6 2. Crawford W. Long . . . , ■ . . . . . 9 3. Horace Wells ........... 11 . 4. William T. G. Morton 12 5. The original Morton inhaler . . . . . . . .13 6. The original Morton inhaler ........ 14 7. One of the earliest operations imder ether at the Massachusetts General Hospital . . 15 8. Charles T. Jackson .......... 17 9. Sir James Y. Simpson ......... 21 10. Bust of Sir James Y. Simpson 22 11. Gwathmey's vapor apparatus with the tube leading from the heater in actual practice ....... 71 12. Gwathmey vapor inhaler with heating apparatus ... 72 13A-C. Boothby Curves 74 13d-e. Boothby Curves .......... 75 14. Oxygen passing through rubber coil immersed in hot water . 89 15. Intra-abdominal administration of oxygen in case of intestinal adhesions .......... 89 16. Suturing of the peritoneum ........ 90 17. Aponeurosis united with inteiTupted sutures .... 91 18. Superficial fascia united ........ 92 19. Tube withdrawn; peritoneal purse-string tied; knot beneath aponeurosis .......... 93 20. Gatch nitrous oxid-oxygen apparatus . . . . . . 104 21. Chart showing pulse and respiration with rebreathing . . 105 22. Chart of the pulse, respiration, and blood-pressure during anes- thesia of two hours and fifteen minutes' duration . . 106 23. Chart showing value of rebreathing during operation . . 107 24. Tracing obtained froni the pyloric ring of a frog suspended in a moist chamber into which ether vapor and carbon dioxid could be passed ......... 114 25. Gardner Q. Colton 119 26. Guedel's apparatus for the self-administration of nitrous oxid and air ........... 138 27. Guedel's apparatus, showing detail construction of respiratory valve • . . . 139 XXV xxvi LIST OF ILLUSTRATIONS FIG. PAGE 28. Diagrammatic sketch showing simple method of administering nitrous oxid and oxygen with indefinite quantities of the agents used .......... 144 29. Davis nitrous ■ oxid-oxygen apparatus ...... 145 30. Davis apparatus case . . 146 31. Davis nitrous oxid-oxygen apparatus with vapor apparatus dis- connected ........... 146 32. Davis nitrous oxid-oxygen apparatus showing heater . . 147 33. Davis nitrous oxid-oxygen apparatus with Gwathmey vapor in- haler 147 34. Davis nitrous oxid-oxygen apparatus with Gwathmey vapor in- haler. With cover 148 35. Davis nitrous oxid-oxygen apparatus with Gwathmey inhaler. Without cover 148 36. Coburn's apparatus with anesthetic table and cylinders attached 149 37. Coburn's apparatus : face-piece and bag ..... 149 38. Coburn's apparatus: face-piece and electric heater . . . 150 39. Gwathmey's nitrous oxid-oxygen apparatus .... 150 40. Gwathmey oxygen Y-piece adapted for Bennett's, Furniss' or Gwathmey inhaler 151 41. Teter nitrous oxid-oxygen apparatus 152 42. The Teter vapor warmer . 153 43. Teter's face mask 154 44. Teter ether attachment 154 45. Teter nasal inhaler 155 46. Teter's auxiliary tube for administering nitrous oxid and oxygen through the mouth ......... 155 47. Teter nitrous oxid-oxygen apparatus with nasal inhaler in use 156 48. Teter nitrous oxid-oxygen apparatus with nasal inhaler in use, with surgeon operating ........ 156 49. Teter's nasopharyngeal tubes for nitrous oxid and oxygen . 157 50. The Ohio monovalve 158 51. Ohio small nitrous oxid inhaler 159 52. Connell's anesthetometer ........ 160 53. Pressure gauges for large tanks of nitrous oxid and oxygen . 161 54. Boothby and Cotton apparatus set up . . . . . . 162 55. Boothby and Cotton apparatus folded 163 56. Boothby and Cotton face-mask 166 57. Gwathmey-Woolsey nitrous oxid-oxygen apparatus . . . 171 58. Gwathmey-Woolsey nitrous oxid-oxygen apparatus with cylinders attached 172 59. Gwathmey-Woolsey nitrous oxid-oxygen apparatus as used in general surgeiy ......... 174 60. Gwathmey-Woolsey nitrous oxid-oxygen apparatus in adenoid and tonsil operations . . 174 61. The pupillometer 195 62. Dropper from original can 200 63a. Chloroform and ether containers for the drop method . . 200 LIST OF ILLUSTRATIONS xxvii FIG. PAGE 63b. Chloroform and ether containers for the drop method . . 201 64. Ether containers with dropper ....... 201 65. Glass container for holding ether 202 66. Lumbard's rubber ether blanket and elastic mask holder . . 202 67. Yankauer-Gwathmey drop and vapor mask ..... 203 68. The Ferguson mask 204 69. Davis dropper for insertion in original container .... 206 70. The ether rausch 210 71A-0. The handkerchief method 213-215 72. Cone adjusted to the face 216 73. Allis inhaler with soft rubber cover for semi-open method . 216 74. Allis inhaler, metal with rubber cushion for face and gauze dia- phragm ........... 216 75. The Esmarch inhaler 217 76. Comparative size of bores of inhalers ... . . . 217 77. Bennett's nitrous oxid-ether apparatus : ether inhaler . . 218 78. Bennett's nitrous oxid-ether apparatus : gas inhaler . . . 218 79. Bennett's nitrous oxid-ether apparatus : gas and ether inhaler . 218 80. The Gwathmey inhaler open ........ 219 81. The Gwathmey inhaler closed . 219 82. Gwathmey nitrous oxid-ether apparatus 220 83. The Fumiss nitrous oxid-ether apparatus 221 84-85. The Davis apparatus showing inhaler for ethyl chlorid-ether sequence by the closed drop method ..... 222 86. Davis apparatus for gas-ether or ethyl chlorid-ether by drop method . . . . . . . . . • • 223 87. Davis heater for ether and nitrous oxid and oxygen . . . 223 88. Davis heater with the Gwathmey three-bottle vapor inhaler . 224 89. Vapor mask 224 90. Top of three-bottle vapor inhaler ....... 225 91. Diagram of top of three-bottle inhaler ...... 225 92. Jackson's speculum in position for the introduction of the endo- tracheal catheter 226 93. Endopharyngeal tubes for maintaining insufflation anesthesia . 227 94. Glass nasal tubes for general anesthesia ..... 227 95. Junker inhaler .......... 228 96. Lumbard's glass nasal tubes 229 97. Three-bottle vapor apparatus connected with electric heater and vapor mask 230 98. Foot pump attached to three-bottle vapor inhaler . . . 230 99. Gwathmey method of administering warmed vapor through the nose 100. Ether vapor mask encircled by a towel held in place by a safety- pin ............ 101. Same as Figure 100 with outer fold of towel dropped as patient reaches surgical anesthesia ....... 102A-B. Methods of holding jaw forward so as to maintain an open airway 233 231 232 232 LIST OF ILLUSTRATIONS PIG. 103. Pinneo's ether vapor apparatus, diseonneeted 104. Pinneo's ether vapor apparatus in use ...... 105. Pinneo's mouth tube for continuous vapor anesthesia . 106. Endopharyilg-eal insufflation and mouth tube combined . 107. Three-bottle vapor appai^atus attached to oxygen tank . 108. Chart I, showing the necessary percentage of ether vapor for the endopharyngeal or endotracheal administration 109. Chart II, showing the most advantageous ether pressure . 110. Administration of warmed ether vapor by the closed method 111. Diagrammatic sketch of the nitrous oxid-ether vapor sequence 112. Sealed tubes of ethyl chlorid 113. Double end ethyl chlorid tube . ... 114. Automatic closing tube for ethyl chlorid 115. Automatic closing tube for ethyl chlorid 116. Flexible spraying nozzle ........ 117. Ferguson's ethyl chlorid tubes for general and local anesthesia 118. The Gebauer container for ethyl chlorid .... 119. Technique of ethyl chlorid measure-dropper . 120. Martin Ware's apparatus for administering ethyl chlorid 121. Ethyl chlorid by the closed method ..... 122. Davis ethyl chlorid-ether inhaler: closed drop method 123. The Pilling chloroform dropper .... 124. A chloroform dropper which should never be used 125. The Roth-Drager apparatus ..... 126. The Roth-Drager apparatus ..... 127. The Roth-Drager apparatus . . ... 128. Vernon Harcourt's inhaler, complete with face-piece, bottle beads 129. Junker's apparatus ...... 130. Hewitt-Mason's mouth-gag with anesthetic tubes 131. The Gwathmey three-bottle vapor inhaler, niouth gag, with hollow tubes attached 132. The water suction apparatus for adenoid and tonsil operations 133. Pump attached to spigot with water turned on . 134A-J. Dr. French's chair table 135. Supporting jaw to maintain free ainvay with two fingers on the carotid artery . . . . . . 136. Preparing to lift patient . . . . 137. Carrying patient head high . . . . 138. Hewitt's artificial airway 139. Ferguson's modification of Hewitt's airway . 140. Connell's breathing tube 141. The Lewis pendulum swing . . . . . 142A-B. Artificial respiration 143A-J. Draeger's pulmotor 144. The lung motor 145. Meltzer's apparatus for artificial respiration with pharyngeal tube and foot belloAvs and 346- 396- PAGE 234 235 236 236 240 241 242 244 245 254 254 254 254 254 255 256 256 273 274 275 312 313 318 319 320 321 321 322 334 343 344 -351 361 377 378 391 391 392 393 395 -399 399 400 tubes LIST OF ILLUSTRATIONS FIG. 146. Meltzer's apparatus for artificial respiration with mask atiaclicd to oxygen tank ....... 147. Blood-pressure tracing from an etherized dog 148. Crile's abdominal hysterectomy chart .... 149. Crile's thyx'oidectomy chart ...... 150. Crile's chart of mortality rate ..... 151. Operations under anoci-association .... 152. Technique of abdominal operation under anoci-association 153. Blood pressure apparatus as used by McKeson . 154. McKeson's blood pressure chart No. 3908 ... 155. Meltzer's simple apparatus for intratracheal insufflation 156. Elsberg's apparatus for hospital use .... 157. Diagram to explain the parts of Elsberg's apparatus No. 1 158. Elsberg's simplified portable apparatus for intratracheal insuf- flation . . . . . . . . . 159. Elsberg's apparatus ....... 160A-B. Janeway's apparatus ...... 161. Fischer's apparatus ....... 162. Ehrenfried's apparatus for intratracheal etherization . 163. Cotton-Boothby introducing cannula, Ehrenfried's modification, for soft rubber tubes ...... 164. Ehrenfried's introducing forceps for stiff or soft rubber 165. Jackson's direct laiyngoscope 166. Elsberg's clip to hold the intratracheal tube in place . 167. Latest form of colonic anesthesia apparatus . . . 168. Apparatus for administering ether per rectum . 169. Apparatus of Ligueu, Morel, and Verliac . . '. 170. Leggett's apparatus ....... 171. Parts of vapor generator . . . . 172. Schematic section of vapor generator .... 173. Sectional view of manometer ...... 174. Sectional view of H-tube ...... 175. Simple form of Sutton's apparatus .... 176. Complete apparatus with oxygen tank . , . . 177. Combination clip with hook . . . . ... 178. Check valve used on afferent tube when coughing is to be permitted 179. Sketch of pipe-line system with safety valve Avater monometer attached . . . . . . . .... 180. Gwathmey rectal irrigating tube 180a. Showing patient in position for oil-ether" administration 181. Sequestration method as used in French's clinic 182. Syringes and solutions bottles for local anesthesia . 183. Showing triangular pad supporting back and sandbag as support of feet ........... 184. Method of applying rubber bandages for Bier's venous anesthesia 185. Syringe and cannula for Bier's venous anesthesia . 186. Beginning of skin wheal ........ 187. Continuation of wheal .... .. . . , . XXIX PAGE 400 401 405 406 406 407 407 411 412 417 419 420 421 422 424 425 426 426 427 428 428 438 441 442 442 445 445 446 447 447 448 450 450 451 461 461 474 481 487 491 491 494 494: XXX LIST OF ILLUSTRATIONS FIG. PAGE 188. Congestion of wheal and beginning of deep injection . . . 495 189. Anesthetization of skin by subcutaneous injection, showing wide area of distribution through two injection points . . . 495 190. Injection of the deeper structures through the same points as in Figure 189 496 191. Nerve supply of face and scalp from the cervical plexus and trigeminal nei-ve ......... 497 192. Showing the area of anesthesia produced by a cross strip of sub- cutaneous injection above the supra-orbital ridge, blocking the nei^e supply from below ....... 498 193. Sensory innervation of the mucous membranes of the head . 499 194. Sagittal section through the foramen ovale ..... 500 195 Position and size of skin wheal for puncture of Gasserian ganglion 500 196. Front and side views showing the direction of the cannula to reach the Gasserian ganglion according to Haertel's method . 501 197. Area of anesthesia produced by blocking the cervical plexus at the posterior border of the sternomastoid muscle . . . 501 198. Blocking the cervical plexus at posterior border of sternomastoid muscle . 503 199. Incision through skin and platysma muscle showing almost blood- less field 504 200. Operation completed; wound closed ...... 505 201. Cross-section of forearm, 5 cm. above the wrist . . . . 507 202. Distribution of the nerves of the upper extremity to the skin anteriorly and posteriorly . 508 203. Cross-section through base of finger 509 204. Cross-section through leg just above ankle, showing direction of needle for perineural injection of posterior tibial nerve . 509 205. Injection of skin incision for hallux vagus . . . . . 510 206. Deep in'ection between metatarsals 510 207. Injection of periosteum 511 208. Resection of bone 512 209. Insertion of fascial flag . 513 210. Anesthetization of prepuce in circumcision 514 211. Anesthetization of base of prepuce in circumcision . . . 514 212 Showing separate injection of fraenum in circumcision . . . 515 213. Anesthetization of anal and rectal regions .... 516 214. Sagittal section of rectum, showing the direction of the needle in anesthetizing the rectum 517 215. Relations of the inguino-scrotal nerves to the hernia incision , . 520 216. Sketch showing usual situation of nerves as exposed after division and reflection of the aponeurosis of external oblique muscle 521 217. Scheme of injection in large umbilical hernia .... 522 218. Holder for arm 525 219. Vein exposed and ligated distally 526 220. Cannula introduced and tied in the vein 527 221A-B. Salvarsan method of introducing the needle .... 528 222. Patient under anesthesia by the intravenous method . . . 530 LIST OF ILLUSTRATIONS xxxi FIG. PAGE 223. Another model apparatus for intravenous anesthesia . . . 531 224. Application of the ethyl chlorid spray 538 225. Outfit for preparing the hypodermic solution .... 542 226. Dental hypodermic syringe ........ 542 227. Method of injection into the labial subperiosteal gum tissue . 544 228. Method of injecting into the palatine subperiosteal gum tissue . 545 229. Subperiosteal injection about an upper cuspid .... 546 230. Subperiosteal injection about an upper molar .... 546 231. Peridental injection about an upper bicuspid .... 547 232. Perineural injection upon the buccal side of the upper jaw . 548 233. Perineural injection upon the hard palate ..... 550 234. Perineural injection near the mandibular foramen . . . 551 235. Operation under way for removal of tumor of abdominal wall under spinal analgesia ........ 573 236. Second operation, same analgesia, same patient as in Figure 235 573 237. Same patient as in Figures 235 and 236. At end of operation 574 238. Enlarged picture of patient's face showing facial expression 575 239. Amputation of foot just above ankle joint under spinal analgesia 578 240. Inguinal hernia, inherent intestine, adhesions being pulled apart under spinal analgesia ........ 579 241. Same as Figure 240, head elevated 579 242. Same patient at end of operation ....... 580 243. Diagram of cross-section opposite the fourth lumbar interspace 606 244. Diagram of a cross-section through the dorsal spine . . . 606 245. Spinal cord enclosed in unopened dural sheath lying within verte- bral canal 608 246. Posterior wall of vertebral canal has been removed and dural sheath opened to expose spinal cord and dorsal roots of at- tached nerves .......... 608 247. Upper part of spinal cord within dural sheath, which has been opened and turned aside 609 248. End of spinal cord with roots of lower nerves descending in cauda equina to gain their respective foramina .... 610 249. Schematic picture showing landmarks used in locating space be- tween third and fourth lumbar vertebrae .... 611 250. Schematic picture showing needle inserted between third and fourth lumbar vertebrae of the spinal canal, but below the cord 611 613 614 251. Patient in sitting posture ready for spinal puncture . 252. Injection being made with patient in recumbent position . 253. Table containing instruments and materials used in giving spinal analgesia 615 254. Bainbridge's syringe and needle ....... 615 255. Babcock's needle for spinal analgesia ...... 615 256. Sterilizing the apparatus . 616 257. Puncture site area painted with iodin 618 258. Sterilizing sheet, patient draped, and window made at site of puncture 619 XXXll LIST OF ILLUSTRATIONS. FIG. 259. Locating the site for puncture . . . 260. Applying ethyl chlorid and incising the skin . 261. Showing direction of needle about to enter spinal 262. Cerebrospinal fluid escaping .... 263. Injecting solution . 264. Cotton and collodion dressing on puncture point 265-268. Myograms No. 5 to No. 8. Unipolar method 269. Myogram No. 9. "Unipolar" 270. Myogram No. 10. "Wireless" . 271. Myogram No. 11. "Wireless" . 272. Tracing No. 1. Made during usual form of caused by intensive chloroforming in a dog 273. Tracing No. 2. Primary cardiac syncope in dog 274. Tracing No. 3. Primary cardiac syncope in dog 275. Suggesting rigidity of the arm . 276. Beginning of sleep by Frink's method 277. Beginning of sleep by Frink's method 278. Induction of anesthesia . 279. Anesthesia in a case of acute mania 280. Apparatus used by Baskerville and Neidle 281. Graph showing the heat generated by mixing ether 282. Graph showing densities of I'esidues . 283. A calibrated pykonometer of 25 c. c. capacity canal apparent and death chloroform PAGE 620 620 621 622 622 623 631 632 632 632 640 640 641 660 661 662 664 668 706 707 709 865 ANESTHESIA CHAPTER I THE HISTORY OF ANESTHESIA Introductory Eemarks: Ancient History; Beginning of the Christian Era; Asiatic Sources; Middle Ages; Hypnotism; Real Be- ginnings of Surgical Anesthesia; Discovery of Ether Anesthesia; The Discovery of Nitrous Oxid for Surgical Anesthesia. Ether: Morton; First Public Demonstration; Letheon; Anes- thesia in England. Chloroform: Theological Opposition to the Use of Anesthetics; The Early Use of Chloroform in Midwifery; Some Physicians Believe in Pain; Prejudice Developed against Chloroform; Scientific Adminis- tration of Ether and Chloroform; Efforts to Overcome Objections to Chloroform by Use of Substitutes and Improved Inhalers; A.C.E. Mix- ture; Substitutes; First Vapor Inhaler; Nitrous Oxid More Generally Appreciated; Nitrous Oxid and Oxygen; Discarding Chloroform for Ether; Improved Methods for Administering Ether; Warmed Ether Vapor; Chloroform Condemned; Medication before Anesthesia; The Use of Chloroform Accompanied with Danger ; Chloroform and Oxygen ; Combinations and Sequences in Anesthetics; Ethyl Chlorid; Impor- tance of Trained Anesthetists. Bibliography, INTRODUCTORY REMARKS Sacred/ profane, and mythological literature abound in incident, fact and fancy, showing that from the earliest times man has sought to assuage grief and pain by some means of dulling consciousness. In these attempts many methods and diverse agents have been employed. The inhalation of fumes from various substances, weird incantations, the external and internal application of drugs and many strange con- ' The Bible and Talmud contain references to the ancient practice of induc- ing sleep by artificial means. 1 2 ANESTHESIA coctions^ pressure upon important nerves and blood vessels, the "laying on of hands" or animal magnetism, mesmerism, hypnotism, and the many methods which come within the pale of modern science, as well as pseudo-science,. have played their part in the evolution of anesthesia. It is intended in this section to give a brief review of what is now known as general, or inhalation, anesthesia. The various other measures for the dulling of consciousness and for the induction of partial or com- plete insensibility to pain are fully discussed under their respective heads, and will be given only scant attention in this connection. Ancient History. — During the classic era of Grecian literature. Homer in his "Odyssey" ^ caused Helen of Troy to put some drug into wine to "lull all pain and anger, and bring forgetfulness of every sor- row." It is not known what constituted Helen's nepenthe, some believ- ing it to have been mandragora, while others maintain it was opium. Five hundred years after Homer, Herodotus, the great historian of Greece, tells of a custom among Scythians of inhaling the fumes of a vari- ety of hemp, which produced an exalted mental state, followed by sleep. The chronicles of ancient Eome furnish similar evidence. For in- stance, these record the utterances of the renowned mythological oracle of Apollo at Delphi, which were probably nothing more nor less than the exaggerated ravings of the priestess Pythea. Her seemingly inspired sayings are attributed to the inhalation of carbon dioxid," which is sup- posed to have been generated in the cavern. Having been removed to the altar before the convulsive stage set in, her mumblings were interpreted by the faithful as the voice of Apollo. The famous Grotta del Cane, near Naples, at the present time furnishes an example of conditions which may have been utilized for just such purposes.^ ■ Beginning of the Christian Era. — That the use of mandragora was well known at the beginning of the Christian era is absolutely certain, for many references to it are made by the writers of that period. Dios- corides, a Greek physician, who lived about the middle of the first cen- tury, and who was for seventeen hundred years an authority on the science of healing, makes what is probably the earliest allusion to its use.'* Galen,^ another Greek and a contemporary of Dioscoridcs, makes mention of the power of mandragora to paralyze sensation and motion. Lucian, in speaking of Demosthenes, says he aroused his fellow citizens, ^Homer's "Odyssey"; 4, 220. ^Memphis marble and vinegar were used as a local anesthetic by the Eomans! * From the sides of the cavern, steam and carbon dioxid emanate in suffi- cient quantities to form a stratum in which dogs are first convulsed and then asphyxiated, while persons who are in a standing position above the stratum are unaffected. * Be Med. Mat., Lib. 4, 76. The root of ' ' atropa mandragora ' ' was boiled in wine and administered prior to surgical operations, = lUd., Lib. 7, 207. THE HISTORY OF ANESTHESIA 3 who were as if put to sleep by mandragora. Roman historians, among tliem Pliny/ also described the use of mandragora from earliest times. The people of their country employed it extensively to relieve the suffer- ing of victims of crucifixion. Asiatic Sources. — Preparations of different drugs were made by the Jews and Chinese, and given to criminals to produce such a mental state that they would confess their crimes, or to make less agonizing the hor- rible tortures inflicted. In view of the fact that it is indigenous to China, undoubtedly the Chinese were the first to use Indian hemp as a means of dulling the con- sciousness of pain. The Egyptians used this herb under the name of "liasliish" The fumes of this, when inhaled, induced intoxication and mental exaltation. A Chinese practitioner of the third century, Hoa-tho, gave to a patient a preparation of hemp, whereby he shortly became insensible "as if he had been drunk or deprived of life." We are told that after a cer- tain number of days the patient found himself "reestablished" without having experienced the slightest pain during the operation. The ancients early noted that volatile substances acted more promptly and effectually when inhaled than other substances taken by the mouth, and inhalation was employed by the Greeks, Eomans, Arabians and Chinese. Middle Ages. — In the thirteenth century, an oil which put patients to sleep on occasions of painful operations was prepared and successfully used by Hugo de LucCa. It consisted "of opium, of the juice of the unripe mulberry, of hyoscyamus, of the juice of hemlock, of the juice of the leaves of mandragora, of the juice of the leaves of wood ivy, of lettuce seeds, of dock seeds, and water hemlock boiled with a sponge, which, 'for use, was soaked in hot water and applied to the nostril." To awaken the patient, another sponge, soaked in vinegar, was applied to the nose. As late as 1534 this "spongia somnifera" was still in use. Shortly after this. Pare referred to it as a practice "used formerly by operators." The uncertain action of this concoction arising from necessary differ- ences in preparation, from the method of application of the vapor, and from the ignorance of the strength of the various ingredients, led to its temporary abandonment. It is difficult to imagine why the preparation of anesthetics was neglected, when medicine was making the rapid progress which marked its development during the sixteenth century. Hewitt ^ states : "In 1589 Giambattista Porta, a surgeon who prac- ticed in Naples, used an essence made from hyoscyamus, solanum, poppy, and belladonna, enclosed in a leaden vessel, and, the lid being opened, the patient would draw in by breathing the most subtle strength of the ' Be Med. Mai., Lib. 35, 94. ^Hewitt, Frederick D.: "Anaesthetics," 4tli ed., 3, 4 ANESTHESIA vapor, so that thereby he would be buried in a most profound sleep, nor be aware of what had been done to him." Shakespeare makes several references to the soporific effects of vari- ous drugs, showing that a knowledge of this quality obtained in his day. Early in the seventeenth century, he makes Cornelius, the court physi- cian, prescribe a drug which "Will stupefy and dull the sense awhile; but there is No danger in what show of death it makes, More than the locking up the spirits a time, To be more fresh, reviving. " It is thus seen that ancient, medieval and modern history furnish numerous examples of the use of drugs and other media which brought about partial or complete unconsciousness. Moreover, it is well estab- lished that the Assyrians accomplished the same end by the compression of blood vessels before circumcision; and in the early part of the seven- teenth century this custom was revived by Valverdi, who compressed the nerves and blood vessels of the parts to be operated upon. Hypnotism. — The foregoing resume of historical references to methods employed in former times needs but the addition of a brief men- tion of the hypnotic effects induced by weird incantations, as practiced by the Egyptians, Persians, Indians, and others. This leads up to the time of Greatrakes, the noted "Irish stroker," who produced sleep as a result of his magnetic touch, or "the laying on of hands." He was prob- ably the most noted advocate of this method prior to Mesmer, the Swiss physician, who, about the middle of the eighteenth century, investigated the phenomena of animal magnetism along scientific lines, applying his researches to curative ends and enunciating a doctrine which became known as "mesmerism," after the founder. Real Beginnings of Surgical Anesthesia. — It was at the close of the eighteenth century that modern surgical anesthesia was foreshadowed, with the discovery of hydrogen in 1766, nitrogen in 1772, and oxygen and nitrous oxid in 1774. "Pneumatic chemistry," as it were, opened up a field of experimentation which made possible surgical operations under conditions which Humphrey Davy described as "uneasiness being swallowed for a few minutes by pleasure." Soon after the discovery of these gases, attempts were made to put them to practical use. In 1785 Pierson, of Birmingham, England, used ether inhalation for asthma, and in 1789 the Medical Pneumatic Insti- tute was organized under Dr. Beddoes, where huge reservoirs of gases were installed for the treatment of phthisis and other diseases by inhala- tion. This Institute, which was superintended by Humphrey Davy, while not successful in itself, was important in that it led to Davy's experiments with nitrous oxid. By 1799 and 1800 Davy had become THE HISTORY OF ANESTHESIA 5 sufficiently well acquainted with this gas to use it for the alleviation of headache and also for the extraction of one of his own wisdom teeth. This latter event led him to make the historic prediction, "Since nitrous oxid seems capable of destroying physical pain, it may be used in surgical operations, where there is no great effusion of blood." The value of this suggestion was not recognized for nearly half a century. Warren, of Boston, used "sulphuric ether" in 1805 on a patient suffer- ing with phthisis, and in 1806 it was used in attacks of asthma. Faraday seems to have been the first to recognize the value of "sulphuric ether" as an anesthetic. In 1818, there appeared a paragraph attributed to Faraday in the Quarterly Journal of Science and Arts, in which it was pointed out that "when the vapor of ether is mixed with common air and inhaled, it produces effects very similar to those occasioned by nitrous oxid." An incident occurred on November 6, 1821, which, had it been cor- rectly interpreted, might have led to an earlier discovery of general anesthesia. On that day. Stockman, of Utica, gave an exhibition in Eome, N. Y., of the effects of nitrous oxid. After the demonstration, the lecturer, on adjourning to a back room, found there a young man com- pletely anesthetized with his mouth to the faucet of the gas tank. He had been stealing the gas for its exhilarating effect and had been over- come by it. The first successful experiments upon lower animals, for the purpose of rendering them insensible to pain by means of the inhalation of gases, were made by Henry Hill Hickman ^ between the years of 1820 and 1828. Hickman was twenty years of age when he became a member of the Eoyal College of Surgeons and began his career as a country practitioner in the little town of Ludlow, Shropshire, England. "Impressed by the agonizing sufferings of those on whom he was called to operate, he resolved to seek some method of alleviating their pain by rendering them unconscious before the operation. With this object, he commenced a series of experiments on animals, first, by pro- ducing semi-asphyxiation by the exclusion of atmospheric air; then by causing them to inhale small quantities of carbon dioxid, and later nitrous oxid gas. After rendering the animals unconscious, he excised the ears, amputated their legs, made incisions, then dressed the wounds, noted the time they took to heal, and the period of their complete recov- ery. He carried on these experiments for some time, and at last met with considerable success. This convinced him that, could he but carry out his experiments on the human subject, his methods would become of the greatest value to mankind in making painless the performance of major surgical operations." ' Henry Hill Hickman : "A Forgotten Pioneer of Anesthesia, ' ' Brit. Med. J., April 13, 1912, 843. 6 ANESTHESIA His notes on some of these interesting experiments are still extant in his own handwriting, of which the following is an extract: "Experiment 1, March 20th. — I took a puj^py a month old and placed it on a piece of wood surrounded by water, over which I put a glass cover so as to prevent the access of atmospheric air ; in ten minutes he showed great marks of uneasiness, in twelve minutes respiration be- came difficult, and in seventeen minutes ceased altogether; at eighteen minutes I took off one of the ears, which was not followed by hemorrhage ; respiration soon returned, and the animal did not appear to be the least sensi- ble of pain; in three days the ear was perfectly healed. "Experiment 2. — Four days after, the same puppy was ex- posed to a decomposition of the carbonate of lime by sulphuric acid. In one minute respira- tion ceased; I cut off the other ear, which was followed by very trifling hemorrhage, and, as be- fore, the puppy did not appear to suffer any pain; in four days the wound healed,. The day after the operation he seemed to require an additional quan- tity of food, which induced me to weigh him, and I found he gained 9 oz., 1 drachm and 24 grains in nine days." While Hickman was successful, he was unable to demonstrate "the results of his experiments before his professional brethren, and every- where he was met with the greatest scepticism and his system was gen- erally derided and condemned as dangerous and useless. . . . Dis- heartened by his failure to secure a hearing from the profession in his own country, he at length resolved to lay the matter before the Eoyal Academy of Medicine in Paris, and drew up a memorial to King Charles X. praying for permission to perform his experiments before the leading medical men of that city." The king sent the letter to the Eoyal Acad- emy of Medicine and notified Hickman. The Academy appointed Gerardin ^ to investigate the matter and report to them. He reported as follows on October 21, 1828 : "Painless Operations. — M. Gerardin reported on a letter written to ^ Grerardin : Archives generales, Paris, 18, 453. Fig. 1. — Henky Hill Hickman. THE HISTORY OF ANESTHESIA 7 His Majesty Charles X. by Mr. Hickman, a London surgeon, in which that gentleman asserted he had discovered a means of performing the most troublesome and dangerous operations without pain. The method consisted in producing temporary insensibility l)y the methodical intro- duction of certain vapors into the lungs. Mr. Hickman had made numerous experiments on animals, and was desirous of obtaining the cooperation of the leading physicians and surgeons of Paris, in order to make the same experiments on the human subject." French surgeons proved to be no more liberal in their attitude than had been their British colleagues. When Gerardin's report was presented only one member (Larry) championed Hickman's cause, offering himself as a subject for experimentation. The other members sneered at the idea proposed by Hickman, and so the young surgeon, disappointed and hopeless, returned to England, where he died a few months later (1829) at the age of twenty-nine. "In this tragic manner the curtain fell upon the life of Henry Hill Hickman, who practically sacrificed his career and gave his life in his attempts to gain recognition for his discovery of a method of producing anesthesia by inhalation and rendering patients unconscious to pain dur- ing severe surgical operations." While the suggestion of painless surgery seemed to be in the air, no one laid definite hold upon it. In 1830, two deaths from nitrous oxid attracted much attention. Each was caused by the breaking of a jar containing the gas in the room where the victim was sleeping. Discovery of Ether Anesthesia. — The efforts of the past culminated in the discovery of inhalation anesthesia, with ethyl ether as the agent, in 1842. The public had gradually become familiar with the inhaling of vapors. It is reported in the Americaii Journal of Science for Janu- ary, 1832, that Ives, of New Haven, used chloroform (see page 281) in medicine. Humphrey's book on "Medicated Vapors" appeared in 1831. At about this time scientific lecturers were in the habit of demonstrating the intoxicating properties of ether on young men ; and many young peo- ple, especially medical students, held wild frolics under its influence, after inhaling it to the point of intoxication. It so happened that these lec- tures and ether parties were directly responsible for the discovery of surgical anesthesia. In 1839, some young people held a quilting party near Athens, Ga., after which they finished the evening by inhaling ether. At the height of the frolic, a negro boy appeared at the door and was invited to partake of the ether, but he refused. Some of the boys dragged him in and forced a handkerchief, covered with ether, to his mouth and nose. After a long struggle he became quiet and the boys desisted. Instead of getting up, the negro lay as if asleep and, much to the terror of 8 ANESTHESIA the culprits, did not awaken until medical attention was given an hour later. The inhalation of ether and also nitrous oxid to the stage of excite- ment was a common occurrence in different parts of the country at this time. It remained for Crawford W. Long/ of Georgia, to intelligently ^ Crawford Williamson Long was born in Daniellsville, Madison County, Georgia, November 1, 1815. His family was prominent socially and in public affairs. Long graduated second in his class from Franklin College at the age of nineteen, and from the medical department of the University of Pennsyl- vania in 1839, after which time he spent one year "walking" the hospitals of New York City. As a student in the University of Pennsylvania he was under the immediate tutorship of George B. Wood. Da Costa ("Crawford W. Long," "Old Penn WeeMy Beview, April 6, 1912) states: "Wood's condemna- tion of the premature reporting of cases and drug actions may have decided Long a few years later to delay in publishing the report of the action of ether. He insisted that observers must never be content with a single experiment. ' ' Woods Hutchinson stated at the unveiling of the monument to Long at Jeffer- son, Georgia, that "His discovery was no accident. His real genius and the proof of his greatness lay in his wisdom to see the possibilities. His courage to attempt experiments, the confidence in his own opinions, and the heartfelt love and sympathy for his suffering patients led him to employ the anesthetic he had discovered not once but many times. He was great in his courage, brav- ing the possibility of the fearful consequences which would have followed failure in those early days of experiment. In many matters he was ahead of his day and generation. He was one of the first to hold that tuberculosis is curable, and that fresh air and diet will effect cures in this dread malady. He added to the sum of human immunity from horror and suffering long before Sir J. Y. Simpson used chloroform for the purpose. ' ' Jackson, in a letter to the Bost. Med. and Surg. J., April 11, 1861, states, among other things, that, "I then called on Profs. Joseph and John Le Conte, then of the University of Georgia, at Athens, and inquired if they knew Dr. Long, and what his character was for truth and veracity. They both as- sured me that they knew him well, and that no one who knew him in that town would doubt his word, and that he was an honorable man in all respects. . . . He is a very modest, retiring man and not disposed to bring his claims before 'any but a medical or scientific tribunal. ' ' The University of Pennsylvania, on March 30, 1912, unveiled a medallion to Long. The state of Georgia has sent his name to Washington, D. C, as one of her two most celebrated sons. Hewitt, Foy, and Buxton, of England, as well as Young, of Johns Hopkins Hospital, all give the credit to Long as the dis- coverer of surgical anesthesia. J. P. Groves, in a letter to Hugh H. Young, of Johns Hopkins Hospital, under date of .January 15, 1897, in giving an account of an operation, states the following : ' ' The patient was placed in a recumbent position on a bed, with the hand to be operated on in front for convenience of the surgeon. Dr. Long poured ether on a towel, and held it to the patient's nose and mouth, too, to get the benefit of inhalation from both sources. Dr. Long determined when the patient was sufficiently etherized to begin the operation by pinching or pricking him with a pin. Believing that no harm would come of its use for a con- siderable length of time, he profoundly anesthetized the patient, then gave me THE HISTORY OF ANESTHESIA make use of facts which were common knowledge to all. Long and his pupils indulged frequently in "ether frolics," during which he was badly bruised, yet he noticed, upon recovery, that he had not been conscious of pain. Frequent observations of this fact, in connection with himself and his students, led Long to conceive the idea of using ether to prevent the pain of surgical oj)erations. When twenty-six years of age, and in the first year of his practice, Long determined to try the ex- periment with ether as soon as possible, and so, on March 30, 1843, he administered ether to Mr. James Venable and re- moved a small tumor from the neck. At the close of the oper- ation the patient assured Long that he had not experienced even the slightest degree of pain. This experiment was so highly successful that Long continued to administer ether in surgical cases, recording about eight such cases between 1842 and 1845. But since his was the narrow sphere of a lo- cal country doctor, his surgical cases were few and his fame did not get beyond the restricted world in which he lived. He made no secret of his discovery, but did not advertise the fact until others had laid claim to the honor. ^ the towel, and I kept up the influence by holding it still to the patient 's nose. The patient was entirely unconscious — no struggling — patient passive in the hands of the operator. ' ' ^ The original bill for services of Long to Mr. Venable is still in existence, and is as follows: James Venable to Dr. C. W. Long, Dr. Fig. 2. — Crawford W. Long. 1842. Jan. Mch. May June 28 Sulphuric Ether $ .25 30 Sulphuric Ether and Exsecting tumor 2.00 13 Sul. Ether 25 6 Exsecting tumor 2 . 00 $4.50 10 ANESTHESIA Long not only used ether upon patients, but behind closed doors he administered it to a medical student, and had the student adminis- ter the anesthetic to him, in order to discover the physiological ac- tion of the drug. Owing to the prejudice and ignorance of the popu- lace, Long was prevented from using ether in as many cases as he might have. In a very scientific spirit he administered ether to a negro boy having two fingers to be amputated, removing one finger under the in- fluence of ether and the second without ether. He did this to prove that insensibility to pain was due to the agent used. "Dr. Long is necessarily deprived of the larger honor which would have been his due had he not delayed years after the universal acceptance of surgical anesthesia. It is also to be regretted that his published details of the mode of administering the ether and the depth of the anesthesia are so meager and unsatisfactory. While the accepted rule that scientific discovery dates from publication is a wise one, we need not in this in- stance withhold from Dr. Long the credit of independent and prior experiment and discovery, but we cannot assign to him any influence upon the historical development of our knowledge of surgical anesthesia, or any share in the introduction to the world at large of the blessings of this matchless discovery." ^ In regard to this point, DaCosta - remarks : "Long has been criti- cised for not publishing his discovery at once. Jenner waited twenty years to publish his and after twenty years had only made twenty-three observations. Suppose someone had published about vaccination after Jenner had worked nineteen years, would Jenner any the less have been the discoverer?" But being far removed from the turmoil and strife that environed the lives of the then three other claimants, Long was not embittered as were the others. He continued to practice medicine in Jackson County, Georgia, and died June 16, 1878, in the sixty-second year of his a,ge. The Discovery of Nitrous Oxid for Surgical Anesthesia. — In 1844, two years and eight months after Long anesthetized the first patient with ether, Horace Wells,^ a dentist of Hartford, Conn., attended a lecture on "Laughing Gas" by G. Q. Colton, a chemist. He noticed (as had Long with ether) that a young man under the influence of nitrous oxid bruised himself very severely, yet was apparently unconscious of pain. Wells had long been studying the question of the painless extraction of teeth, and had previously reasoned that, if excitement from ordinary causes could make one indifferent to pain, the same would probably be true of artificial excitement. ^ Welch, William H. : "A Consideration of the Introduction of Surgical Anesthesia, ' ' 9. ^ Loc. cit. ^Horace Wells was born in Hartford, Windsor Co., Vt., Jan. 21, 1815. THE HISTORY OF ANESTHESIA 11 This incident impressed upon him the l)elief tliat the administration of nitrous oxid would bring about the result for whicb be bad been looking. He planned to test his conclusions oji himself. The next day, December 11, 1844, Colton was called in to administer the gas, and, while Wells was under its influence, Riggs extracted one of his teeth. On recovering consciousness. Wells was so en- thusiastic over the success of the operation that he made plans for its immediate use, and there- after daily extracted teeth under its influence. Early in 1845, he went to Boston in order to lay the matter before the hiedical profession. He gave a public demonstration before the Har- vard Medical College, but be- cause he did not understand the proper administration of the gas — probably because he did not use a sufficient volume — the demonstration failed. Wells was a sensitive man, and this public failure overwhelmed him and he felt himself dis- graced. He continued to ad- minister gas in private practice for some time, but eventually gave up dentistry altogether. In 1847 his reason gave way and, early in 1848, he died by his own hand. Fig. 3. — Horace Wells. ETHER On witnessing one of Wells' operations, H. 0. Marcy remarked that as a student he had found that nitrous oxid and the vapor of "sulphuric ether," when inhaled, produced exactly the same effects. Wells had tried ether, but, owing to the choking sensations jDroduced, resolved to adhere to nitrous oxid. Morton. — It was left, however, to William T. G. Morton, a former pupil of Wells, to place the use of ether as an anesthetic upon a sound basis. His discovery was entirely independent of that of Long, who had preceded him four years.^ ^"William Thomas Greene Morton (Patton, J. M. : ''Anesthesia and Anes- thetics," 17) was born in Massachusetts, studied dentistry in Baltimore, and 12 ANESTHESIA First Public Demonstration. — The first public demonstration of surgery without pain was given in the Massachusetts General Hospital, was a successful practitioner in Boston. He experimented with drugs and with hypnotism in con"neetion with the painless extraction of teeth, and, as we have seen, was associated with Wells in his investigations of nitrous oxid. After the public failure of the experiment of Wells, he abandoned gas and tried 'chloric ether' with unsatisfactory results. At the suggestion of his preceptor, Charles Jackson (Morton being at that time a student of medicine), a physician of Boston, but best known as a geologist and chemist, he experimented with sulphuric ether, beginning his experiments on animals. ' ' In connection with his experiments upon animals Mor- ton 's wife writes : ' ' Every spare hour he could get was spent in ex- periment. He used to make experi- ments nearly every day on ' Nig, ' a black water spaniel, a good-sized dog that had belonged to his fa- ther. His clothes seemed always saturated with the smell of ether. One day he came running into the house in great distress (for he was always tender-hearted), lead- ing the dog, which walked rather queerly, and said, 'Poor Nig, I have had him asleep a long time; I was afraid I had killed him.' " Morton stated to his wife, ' ' The time will come, my dear, when I will banish pain from the world. ' ' ' ' At this time he used to bottle up all sorts of queer bugs and insects until, the house was full of crawling things. He would administer ether to all of these little creatures and especially to the big green worms he found on grapevines. ' ' His friends laughed at these experiments, but Morton replied, "I shall succeed. There must be some way of deadening pain. ' ' It was after this that he began experimenting upon himself. "His success in this direction encouraged him to make a personal experiment, and, in September, 1846, he inhaled ether from a handkerchief while sitting in his operating chair. He was unconscious for several minutes, and, on regain- ing consciousness, he was so elated by his success that he decided to again in- hale the drug and submit to an extraction while under its influence. At this moment the door bell rang and he admitted a man named Eben Frost, whose face was bandaged and who was in that state of mingled hope and consterna- tion so familiar to all dental surgeons. He asked if it were not possible to mesmerize him, and readily consented to inhale ether when assured that it was superior to mesmerism. To the joy of the operator and the astonishment of the patient, the attempt was perfectly successful." Elizabeth Morton: "The Dis- covery of Anesthesia," McClure's Magazine, Sept., 1896. £ ^ , i i Wf f I ^ s. ^^^ "J'^'^ m Fig. 4. — William T. G. Mf)HTON. THE HISTORY OF ANESTHESIA 13 in the presence of the surgical and medical stall; in the c:rowded amphitheater, on October 16, 1846. "Sulphuric ether" was used on this occasion, though Warren used "chloric ether" ^ thereafter, and pre- ferred it. "It was a trying moment to this medical student when he determined to exhibit his discovery of practical ether anesthesia before his class- mates, professors, and the public. But so convinced was he, by reason of his experience gained in private practice, of success, that he was will- FiG. 5. — The Original Mohton Inhaler. ing to face this ordeal. Morton came into the amphitheater late, delayed by waiting for the completion of a new inhaler. Just a few minutes before. Dr. Warren had remarked, 'As Dr. Morton has not arrived, I presume he is otherwise engaged,' apparently conveying the idea that Dr. Morton was not likely to appear. As he was about to proceed with his operation Morton entered. Amidst that sea of faces he saAv not one which was sympathizing. Blank incredulity, or, at the best, curiosity, alone was to be seen. Warren, turning to him, remarked: 'Well, sir, your patient is ready.' Adjusting his apparatus, Morton calmly admin- istered the anesthetic and, turning to Dr. Warren, said : 'Dr. Warren, your patient is ready.' The silence of the tomb reigned in the large amphitheater while Dr. Warren made his first incision through the skin and dissected out a large tumor, while the patient made no sign nor moved a miiscle of his body. When the operation was completed. Dr. Warren turned to the audience and said slowly and emphatically : 'Gen- ^See Baskerville and Hamor: J. Ind. Eng. Chem., 4, No. 3. 14 ANESTHESIA tlemen, this is no humbug,' and Bigelow remarked, 'I have seen some- thing to-day that will go around the world.' " ^ Operations under ether followed quickly, and from that time its use as an anesthetic sj^read rapidly throughout the world. It is almost inconceivable to those who now witness operations daily under anesthesia to appreciate what it really means to the patient and to those who are compelled to be present. No one has brought this out more forcibly than Hayden,^ in an article in which he gives a description of an operation previous ' In July, 1868, Morton left his home for New York to reply to an article that had recently appeared in one of the monthlies advocating Jackson's claim to be the discoverer of ether anesthesia. His wife states that this article "agi- tated him to an extent she had never seen before. ' ' It was extremely hot, and after reaching New York he telegraphed his wife that he was ill and for her to come. Under the treatment of the dis- tinguished Sayre, Morton rapidly im- proved and he attempted to drive his wife to a hotel on Washington Heights as a change from the hot city. On the way through Central Park he complained of feeling sleepy, but refused to give his wife the reins or to turn back. Sud- denly he sprang from the carriage and stood on the ground, apparently in great distress. He quickly lost consciousness, and his wife called upon a policeman and Swann, a druggist, who assisted in placing Morton upon the grass, but he was past hope of recovery. He was taken at once to St. Luke 's Hospital, but was dead by the time he reached there. At the time of his death he was forty- eight years of age. He was buried in Mount Auburn Cemetery in Boston in the presence of many noted physicians. Over his tomb an inscription written by Jacob Bigelow is placed, which states: "William T. G. Morton, Inventor and Eevealer of anesthetic inhala- tion, by whom pain in surgery was averted and annulled; before whom, in all times, surgery was agony; since whom, science has control of Fig. 6. — The Original Morton Inhaler. pain. 'Hayden, William E. : Inter. J. Surg., 1896. THE HISTORY OF ANESTHESIA 15 to the introduction of an<3sthesia, and of operations as they arc conducted at this time. "With a meek, imploring look, and the startled air of a fawn, as her modest gaze meets the bold eyes fixed upon her, she is brought into the amphitheater crowded with men, anxious to see the shedding of her blood, and laid upon the table. With a knowledge and merciful regard Fig. 7. — One of the Earliest Operations under Ether at the Massachusetts General Hospital. as to the intensity of the agony which she is to suffer, opiates and stimu- lants have been freely given her, which, perhaps, at this last stage, are again repeated. She is cheered by kind words and the information that it will soon be over, and she freed forever from what now afflicts her; she is enjoined to be calm, and to keep quiet and still, and, with assis- tance at hand to hold her struggling form, the operation is commenced. "But of what avail are all her attempts at fortitude? At the first clear, crisp cut of the scalpel, agonizing screams burst from her, and, with convulsive struggles, she endeavors to leap from the table. But force is nigh. Strong men throw themselves upon her and pinion her limbs. Shrieks upon shrieks make their horrible way into the stillness of the room, until the heart of the boldest sinks in his bosom, like a lump of lead. 16 ANESTHESIA "At length it is finished, and, prostrate with pain, weak from her exertions, and bruised by the violence used, she is borne from the amphi- theater to her bed in the wards, to recover from the shock by slow degrees." Now "How would the same case be now? With a sweet, calm smile play- ing around her mouth, — an evidence of pleasant dreams, — her eyes fast closed as in a gentle sleep; her body extended languidly and listlessly as in the repose of childhood, surrounded by no ill-favored men whose powerful aid will be needed; with no crowd of medical men to guard against unforeseen accidents. The surgeon, and his two assistants to pass the necessary implements, or to assist in stanching the blood, are all who are required. At his leisure — not hurried by the demands' of pain to complete as soon as possible — he can coolly prosecute his work, varying it to suit any exigency of the occasion, and ready to profit by any favorable contingency which its course may present. "When finished, and all is in that proper condition which will demand no fresh interference for some time, the patient is awakened from her slumber, and receives the glad information that it is all over, and she is to be tortured no more. The one grateful look which answers this news can have no value placed upon it. Alone, it is worth a lifetime of exer- tion and trouble." The formal announcement to the medical profession of this discovery was made by H. J. Bigelow ^ in a paper read before the Academy of Arts and Sciences, on November 3rd, and before the Boston Society of Medical Improvement, on November 9 th, and published in the Boston Medical and Surgical Journal, November 18, 1846.^ Letheon. — On October 27, 1846, Morton and Jackson sought to patent their anesthetic under the name of "Letheon." From its odor it was soon recognized as "sulphuric ether." ^ Not long afterwards Jack- ^ Bigelow {Boston Med. and Surg. J., Nov. 18, 1846) called attention to the experiments which he conducted for the purpose of ascertaining the nature of "Letheon." His first experiment was with sulphuric ether, the odor of which was easily detected in Morton 's preparation. -Patton, Joseph M. : "Anesthesia and Anesthetics," 18. ^ J. F. B. Flagg, M.D., D.D.S., one-time Professor of Anatomy and Physi- ology in the Philadelphia College of Dentistry, "was particularly prominent as having announced to the dental and medical world that the so-called 'Letheon' of Mr. Morton, of Boston, was simply washed sulphuric ether, thus securing to them an unpatentable material." Med. and Surg. Reporter, Phil., Dec. 7, 1872. Flagg (Flagg, J. F. B.: "Ether and Chloroform," Phila., 1851), in re- viewing briefly the history of the inhalation of ether, says: "The surgeons of Massachusetts General Hospital, together with a few initiated, become aston- ishingly fervent in their praises of an 'Invention,' which required the com- bined efforts of scientific attainments and mechanical skill to develop. Clas- THE HISTORY OF ANESTHESIA 17 son resigned his interest in the "invention" and attempted to show that he alone was the discoverer of anesthesia by ether. While he was writing his contentions to the French Institute, Horace Wells went in person to claim the honor of be- ing the real discoverer of anes- thesia, and thus a three-sided controversy was begun. "Partly with a view of keep- ing his discovery out of the hands of persons who might use it unwisely, and acting upon the advice of Eufus Choate and Ca- leb Gushing, lawyers of national reputation, Dr. Morton patent- ed his application of sulphuric ether." ^ While Morton probably had the right to patent his discov- ery, the fact that he did so was most regrettable, for the patent right caused much dissatisfac- tion and adverse comment. Many refused to accept it on the grounds of quackery. One year after its discovery, 1847, one of the largest hospitals in North America had not tried it at all. When Europe confirmed the efficacy of ether, the opposition subsided. sieal erudition came to their aid, and, for a season, good, old 'sulphuric ether' was made to succumb to the name of 'letheon. ' "A circular is broadly cast through the length and breadth of the country, announcing that a compound has been discovered, which, by breathing into the lungs, induces so deep a slumber as to enable us to perform the most painful surgical operations with entire unconsciousness on the part of the patient. In connection with this announcement are the names of Dr. Jackson and Dr. Mor- ton, as its combined (?) discoverers. "A patent is sought, and, under the protection of a caveat, agents are ap- pointed to traverse the country, selling to all, who will buy, the right to use the compound. Thus qualifying everybody and anybody in the use of this powerful agent that would pay the sum of "In cities over 150,000 inhabitants, $200 for seven years. "In cities over 50,000 and less than 150,000, $150 for seven years. "And so on, down to "In cities under 5,000, $37 for seven years." ^ Morton, Mrs. Elizabeth Whitman : ' ' The Discovery of Anesthesia, ' ' Mc- Clure's Magazine, Sept., 1896. Fig. 8. — ^Charles T. Jackson. 18 ANESTHESIA In 1849 Morton petitioned Congress for a reward for his discovery. He was at once opposed by Jackson and the friends of Wells, who was then dead. The celebrated ether controversy thus begun occupied the attention of Congress for many years, and was characterized by the greatest animosity between these former bosom friends and com- panions. Jackson's name is most closely associated with his claim to priority in the discovery of the anesthetic properties of ether, which M^as the sub- ject of a long controversy, that was very painful to him. His claim was supported by the testimony of Francis Alger, J. B. S. Jackson, Martin Gray, and T. T. Bouve, to whose eulogy before the Boston Society of Natural History we are indebted for most of the facts given here- with. These gentlemen were his chosen friends, and were for a long time closely associated with him. J. B. S. Jackson was one of the signers of a remonstrance addressed to Congress against its making a grant of money to W. G. Morton, Jackson's rival in the claim of discovery, based upon the ground that the signers believed that the reward, so far as the question of discovery was concerned, ought to go to Jackson. Martin Gray published a pamphlet under his own name, maintaining that Jack- son was the sole discoverer of anesthesia, and that Morton could only be considered to have performed a secondary part by proving that the ad- ministration of ether is safe in surgical operations. Bouve, who was for a considerable time a student in Jackson's laboratory, and afterward met him frequently in social intercourse, accorded to him the honor of having been the discoverer of the anesthetic properties of ether, but "never thought him entitled to the credit of its introduction into use, or even to that of having thoroughly verified what he claimed to be true respect- ing the safety of administering it. He had experimented upon himself, and had afterward demonstrated respecting it, even going so far as to recommend its use by others, and this constituted discovery ; bvit he did not prove to others what he was himself convinced of, and allowed precious time to pass — yes, much time — without making any application of the discovery. Indeed, had it not been that Mr. Morton sought from him means to prevent pain when extracting teeth, it is doubtful if the world would have had the advantage of the discovery for years, if ever. The truth is. Dr. Jackson was a great genius and had remarkable intui- tive perceptions of scientific truths, but, from some peculiarities hard to comprehend, he often contented himself with enunciating what he recog- nized as fact, without striving to substantiate it. He himself admitted his shortcomings in this respect. When Dr. Gray had written his essay upon the discovery of ether, claiming for Dr. Jackson all the merits of its introduction, I objected to his view of the matter, and took the ground that the world was indebted to both Jackson and Morton for the great boon ; to one as the scientific discoverer and suggester of its use in THE HISTORY OF ANESTHESIA 19 surgical operations, to the other for his application of it and its practical introduction. "Dr. Jackson, learning of this, upon meeting me remarked that I was thought not to be friendly to him in the matter. I then said : 'Doctor, you have known for a long period what Mr. Morton is now demonstrating to be true, but have allowed it to remain a dormant fact in your mind. If he had not sought information from you, might it not have remained so for some years longer?' He answered that possibly it might. I think it may fairly be said that without both Jackson and Morton the world might have been none the happier for what either would have done ; one supplemented the other. To them together belongs the great honor of having served humanity beyond what language can express." ^ 'Tor five years Long refused to take part in the conflict, but finally, in 1854, persuaded by his friends that in that way alone could he obtain recognition of his claims, he wrote to Senator Dawson giving an account of his work. It seems that Dawson was a friend of Jackson, for he wrote to him of this new claimant and requested him to investigate his case. This Jackson did, calling upon Long at his home in Athens on March 8, 1854. "Dr. Jackson finally acknowledged the justice of Dr. Long's claims and wrote to Senator Dawson to that effect. "On April 15, 1854, the appropriation bill ^ was up before the Senate for its final reading. The friends of Wells and Morton, relying on the volumes of manuscript they had presented, were confidently awaiting the result, when Senator Dawson arose and said that he had a letter from Jackson which acknowledged that a Dr. Long in Georgia had undoubt- edly used ether before any of the claimants for the appropriation. "Coming as it did from so prominent a contestant, this announce- ment fell like a thunderbolt on the rival claimants, and from that time they seem to have lost all hope of gaining the reward, and passively allowed the bill to die. "Desirous only of preventing another from being recognized by Con- gress as the discoverer, and not wishing any pecuniary reward himself. Long never pushed the matter farther, and his documents of proof were never even brought up before Congress." ^ Anesthesia in England. — Bigelow took some ether with him to Lon- don and the first operation (extraction of a tooth) was performed on December 19, 1846, at the home of Bott, of Gower Street.* Two days "^Pop. Sci. Mon., 1881, 19, 405. " The bill proposed to appropriate $100,000 as a recompense to the real dis- coverer. ^ Young, Hugh H. : "Long, the Discoverer of Anesthesia," read before the Johns Hopkins Hospital Historical Society, Nov. 8, 1896. *A very interesting account of the first major operation under ether in Eu- rope is given by Dr. F. W. Cock in the University College Hospital Magazine, 20 . ANESTHESIA later, ether was administered to patients at the University College Hos- pital by Squires, Liston operating. In 1847, J. Y. Simpson, a Scottish physician, first used ether in midwifery, and, finding that the pains of labor might be wholly abolished without interfering with uterine con- tractions, adopted it in his obstetric practice. CHLOROFORM On March 8, 1847, Flourens pointed out the anesthetic qualities of chloroform and ethyl chlorid, but his observations did not attract gen- eral attention. During the same year Simpson,^ who had not been entirely satisfied with ether on account of its irritating qualities, incon- venience of administration and odor, consulted Waldie, a chemist of Liverpool. The latter suggested the use of chloroform, of which "chloric ether" was an alcoholic solution. The vapor of "chloric ether" had been previously used as an anesthetic with little success, but when Simpson had obtained the chloroform from Edinburgh and experimented with it, on November 4, 1847, he was more than satisfied with its anesthetic qualities. Thereafter he tried it in obstetric practice with success.^ as follows : ' ' Dr. Bott, a general practitioner of Gower Street, W. C, informed Eobert Liston, the surgeon of University College Hospital, or rather North Lon- don Hospital, as it was then called, that he had used ether successfully on a dental case in his own house. Liston sought the aid of Peter Squire, the well known chemist of Oxford Street, in order to fashion an apparatus for adminis- tering ether, and the inhaler was first tried on his nephew, William Squire. The latter, profiting by the experience on himself, gave the anesthetic to Liston 's patient. The patient was a man of thirty- six years suffering from disorganized knee-joint, and it was decided to amputate. The mouthpiece was applied by Squire and the patient soon sank into insensibility. William Cadge, Liston 's junior, compressed the femoral artery, and Eansome, the house surgeon, held the limb. Liston rapidly completed the operation in twenty-five seconds, accord- ing to Palmer, the dresser. The inhalation had been stopped as the operation was begun. On coming round, the patient tried to lift himself, and asked when the operation was going to begin. On being shown the stump he fell back and wept. Liston. acknowledged the success of the new anesthetic by the remark, ' The- Yankee dodge, gentlemen, beats mesmerism hollow. ' This was a sarcastic hit at Dr. Elliotson, a physician of the same hospital, who practiced the occult art in connection with medicine. The notes of this ease are still extant. The dresser, who wrote them, remarks that not the slightest groan was heard from the patient, nor was his countenance at all expressive of pain. ' ' ^ J. Y. Simpson was born at Bathgate, Linlithgowshire, Scotland, June 7, 1811. In 1832 he received the degree of Doctor of Medicine. On Nov. 4, 1847, he dis- covered the anesthetic properties of chloroform, and made known the fact in a paper on Nov. 10, 1847. He received the highest honors from the British Gov- ernment for this discovery. He died at Edinburgh, Scotland, May 6, 1870, in the fifty-ninth year of his life. -Simpson, Sir James: "New Anaesthetic," 1847, 7; Illustrated London News, Dec. 4, 1847, 370-2. Simpson, E. B., Century, 25, 412; Liv. Age, 66, 720; THE HISTORY OF ANESTHESIA 21 On November 10, 1847, the slow but steady progress of the use of ether received an effectual setback by the publication of Simpson's famous pamphlet on a "New Anaesthetic Agent as a Substitute for Sul- phuric Ether in Surgery and Midwifery." Because of Simpson's writing and his efforts in behalf of chloroform, the use of this new anesthetic spread with remarkable activity, and soon had almost entirely supplanted _ ether in general surgery. Its prog- ress was hastened also by its ease of management and speedy action, and because its vapor was much pleas- anter to take than that of ether. Theological Opposition to the TJse of Anesthetics. — One of the most singular struggles of medical science during modern times oc- curred in our own days and in a Protestant country. Just as there residted a theological and sectarian condemnation of and opposition to inoculation, vaccination, and the use of coca and quinin, so did the ad- vocacy of the use of anesthetics in obstetrical cases by James Young Simpson meet with a vigorous storm of protest. The hostility of the Scotch ecclesiastical authorities to the alleviation of pain in childbirth had its source in an old belief in Scotland. In 1591, for example, a lady of rank, one Euf ame Macalyane, was charged with seeking the assistance of Agnes Sampson for the relief of pain at the time of the birth of her two sons, and was accordingly burned alive on the Castle Hill of Edin- burgh ; ^ and this view, which stood for nothing kind, merciful, or hu- mane, persisted even to the middle of the nineteenth century. Simpson's use of chloroform was denounced from the pulpit as impious and contrary to Holy Writ; and Biblical texts were numerously cited, the general declaration being that to use chloroform was "to avoid one part of the primeval curse on women." As in the time of witchcraft, so strong was the power of the church, so universal the belief in the guilt of all women, that, notwithstanding the fact that Simpson wrote pamphlet after pam- Mon. J. Med. Sci., Sept., 1847; Ednb. Medico-CMr. Soc, Nov. 11, 1848. J. T. Simpson's "Anaesthesia," 1849, 93, 145, 182, 193, 203. Chloroform of the density 1.48 was used by Simpson in 1847. 'Dalyell's "Darker Superstitions of Scotland," 130, 133. Fig. 9. — Sir James Y. Simpson. "To whose genius and benevolence the world owes the blessings derived from the use of chloroform for the relief of suffering." 22 ANESTHESIA phlet to defend the blessing he had introduced, he seemed about to be overcome, when he seized a new weapon, which was, according to White,^ probably the most absurd by which a great cause was ever won: "My opponents forg-et," he said, "the twenty-first verse of the second chapter of Genesis; it is the record of the first surgical operation ever per- formed, and that text proves that the Maker of the universe, before He took the rib from Adam's side for the creation of Eve, caused a deep sleep to fall upon Adam." We are told that this was a stunning blow, but that it did not entirely kill the sectarian opposition, for the leaders of the resistance had strength left to maintain that the "deep sleep of Adam took place be- fore the introduction of pain into the world — in a state of innocence." However, Thomas Chalmers, a new champion, now intervened, and, with a few pungent remarks, dis- persed the enemy forever, and the greatest victory of science against sufi^ering was gained.^ When anesthetics were first used in obstetrics in the United States, prominent New England clergymen also assailed their administrators as having sacrilegiously thwarted "the curse," but such "impious frustra- tion of the curse of the Almighty upon woman" ^ began to be regarded as the greatest boon ever conferred by science upon mankind, shortly after the vigorous support of Chalmers in Scotland. The Early Use of Chloroform in Midwifery. — The records of the Dublin Lying-in Hospital show that the mortality with anesthesia was one in three hundred and twenty, and that the women were delivered within two hours from the commencement of labor. Without anesthesia, the average labor case was twenty hours with a mortality of one in eleven. Some Physicians Believe in Pain. — In spite of these statistics, we find some doctors pleading earnestly against anesthesia in those days. "Pain during operations is in a majority of cases even desirable, and its prevention or annihilation is, for the most part, hazardous to the ^"A History of the Warfare of Science with Theology," 1908, 2, 63. = Duns' "Life of Sir J. Y. Simpson," 1873, 215-222; 256-260. ^ For the views of an enlightened woman on this question, see Matilda Joslyn Gage's "Woman, Church and State," 241, 242, 244 and 433. Fig. 10. — Bust of Sir James Y. iSimpsoh. (In the National Gallery, Edinburgh, Scotland.) THE HISTORY OF ANESTHESIA 23 patient." A French physiologist stated that it was a trivial matter to suffer, and a discovery whose object was to prevent pain was of a slight interest only. Prejudice Developed against Chloroform. — Until January 28, 1848, chloroform was believed to be a safe anesthetic, but the death of a young woman on that day, while under the influence of chloroform, and several other deaths not long after, gave good cause for the suspicion that the drug might be more dangerous than at first supposed. Scientific Administration of Ether and Chloroform. — John Snow, believing that in a too concentrated vapor of chloroform lay the danger, invented an inhaler in 1847 which was designed to regulate the per- centage of vapor. After several years of experience with anesthetics, he published, in 1858, as the result of his experiments, the first attempt to place the administration of ether and chloroform upon a scientific basis. He was the first to describe the effect of inhaling definite percentages of chloroform vapor and air, and experimented to discover the manner in which death occurred under chloroform, ether, and other anesthetics. He came to the conclusion that chloroform caused death by primary cardiac paralysis, due to the inhalation of a too concentrated vapor. Efforts to Overcome Objections to Chloroform by Use of Substitutes and Improved Inhalers. — Because of his belief in the dangers of chloro- form, Snow investigated amylene'^ as an anesthetic and was the first to administer it. His death checked considerably the advance in the scien- tific investigation of anesthetic agents. J. T. Clover, a worthy successor of Snow, was the first to improve the principle of chloroform administration. He published, in 1862, an account of his chloroform inhaler, by means of which the percentages of chloroform and air could be more accurately regulated than hitherto. "A.C.E. Mixture." — The agitation of the question of the physiologi- cal effects of anesthetics caused an investigation to be made by a Com- mittee of the Eoyal Medical and Chirurgical Society of Great Britain. This Committee, appointed "to inquire into the uses and the physiologi- cal, therapeutical, and toxicological effects of chloroform," reported in 1864. They agreed with Snow that the concentrated vapor of chloro- form was dangerous, and, because of the inconvenience of the adminis- tration of ether, recommended the "A.C.E. mixture" as a substitute. This was originally used by George Harley and was composed of alcohol, one part, chloroform, two parts, and ether, three parts. The committee also urged the free admixture of air as of first importance. A detailed account of this and other mixtures will be found in Chapter XX, p. 688. Substitutes. — Two or three new anesthetics were introduced about this time, but while they may have been favorably received in certain ' See Chap. XX, p. 698. 24 ANESTHESIA circles, and for a limited period of time, they never gained general favor. In 1861, "Kerosolene" was introduced in Boston by Dickinson, Bow- ditch, and Merrill. In 1867, Benjamin Eichardson introduced "bichlorid of methylene.". For a time many surgeons were very enthusiastic over the drug, claiming that it had fewer drawbacks than any other. Amer- ican surgeons were not so enthusiastic, believing that its dangers differed only in degree from those of chloroform. First Vapor Inhaler. — On November 30, 1867, in an article in the Medical Times and Gazette, Junker described a very ingenious appar- atus for the administration of chloroform, especially valuable in opera- tions on the nose, throat, or mouth. Nitrous Oxid More Generally Appreciated. — For nearly twenty years little was heard of nitrous oxid, but in 1863, because of the efforts of the same Colton from whom Wells had received his first inspiration, nitrous oxid began to regain the ground it had lost. In that year, Colton formed an association of dentists to perform operations with the use of nitrous oxid, and by 1867 had recorded 20,000 administrations without an accident. These results strongly attracted the dental profession. Eymer, of London, administered the gas successfully there in 1864, and in 1867 Colton demonstrated in Paris before Evans, an American dentist. This led to its general intro- duction into England, for, during the following- year, Colton had his own apparatus taken to that country by Evans, who administered the gas before the Dental Hospital of London. On Dec. 7, 1868, a joint committee of the Odontological Society and the Dental Hospital issued a report which favored nitrous oxid so highly that it has since held the highest position among the anesthetics of modern dentistry. The analgesic properties of nitrous oxid in dentistry are of recent develop- ment. Nitrous Oxid and Oxyg'en. — In 1870, Colton published a pamphlet showing the result of the physiological action of the gas in its practical application to the original discoveries of Davy, Wells, and others. A long step toward making nitrous oxid more practicable was taken in 1868, when E. Andrews, of Chicago, reported for the first time the use of a mixture of nitrous oxid and oxygen with most satisfactory results. He published accounts of several cases, in which, by mixing oxygen with nitrous oxid, he had obtained a more satisfactory form of anesthesia than with nitrous oxid alone. But since the medical profession had always insisted on the exclusion of air, Andrews failed to get the notice he deserved. The late Paul Bert, ten years afterwards, again drew attention to the same procedure. In order to overcome its too feeble action, the large amount of gas necessary, and the limited time during which anesthesia could be pro- duced, Bert gave a mixture of nitrous oxid and oxygen (85: 15) under THE HISTORY OF ANESTHESIA 25 increased atmospheric pressure. He argued that the pressure was necessary in order to have a uniform mixture of the gases, but Hewitt and others believed that pressure was not essential. Bert's apparatus for positive pressure was tried with only partial success, it being too cumbersome and expensive. Hewitt states that the most recent and best development in modern anesthetics is the combination of oxygen with nitrous oxid, producing a non-asphyxial and absolutely safe form of anesthesia. Discarding Chloroform for Ether. — During the year 1870 Simpson wrote to Bigelow in Boston: "Chloroform is the greatest triumph of all, for it has, if not entirely, yet nearly entirely, superseded the use of 'sulphuric ether.' " In spite of this statement, the use of ether had, in the main, held its position against chloroform in the United States. In 1890, after twenty years filled with records of accidents from the use of chloroform, surgeons all over the world began to discard it for ether. Improved Methods for Administering Ether. — Pollack, Warrington, and Hayward warned against the use of chloroform, and Clover's experi- ments did not lead him to the belief that chloroform could be made as safe as ether. He became less and less inclined to use it, substituting nitrous oxid in minor operations. He improved the methods for ad- ministering the latter gas and introduced its use as a preliminary to ether. Clover also discovered the proper principles of ether adminis- tration, and pointed out the advantages of air limitation during the etherization. In 1876, he published an account of his apparatus for the administration of nitrous oxid and ether, either separately or in succession. Warmed Ether Vapor. — The introduction of Clover's portable regu- lating ether inhaler in 1877 went a long way toward solving the question of the rapid and safe administration of ether. This inhaler has gained a wider reputation than any other apparatus of its kind. Its use has shown the value of warmed ether vapor with regard to after-effects. Chloroform Condemned. — During this year, 1877, Clover adopted "bichlorid of ethidene" (ethylidene chlorid), which Snow had used in 1851; but, since a death resulted from it, it did not gain favor. The report of the "Glasgow Committee" of the British Medical Association, issued in 1879, agreed with Snow and his followers in stating that blood pressure and heart action under chloroform were distinctly reduced; and while, where fatalities occurred, respiration usually ceased first, the heart might be primarily paralyzed. The report of the First Medical Association Committee, issued in 1880, stated that many deaths from chloroform were clearly proven to be the result of carelessness or igno- rance. Chloroform was condemned and ether also, though in a less marked degree. The committee recommended "bichlorid of ethidene," but this drug is now practically unknown. 26 ANESTHESIA The dispute reached such proportions that, in order to settle it, the Hyderabad Chloroform Commission was appointed in 1889. This was financed by the Nizam of Hyderabad at the suggestion of Surgeon- Major Lawrie, whose views had long been with the Edinburgh School. After numerous experiments, the commission filed a report agreeing entirely with Syme and the supporters of chloroform. The conclusions thus stated were not accepted by the medical profession generally, and so a second Hyderabad Commission was appointed, the Mzam again supplying the funds. This time experiments were carried on upon a larger scale, and observations were made on many of the lower animals ; but the report, issued in 1891, was a corroboration of the conclusions reached by the First Commission. Medication before Anesthesia. — In 1881, Alexander Crombil, Sur- geon at the Calcutta Medical College Hospital, strongly advocated a combination of the use of morphin and chloroform. He said that he had never seen a death from chloroform, and ascribed his success to the use of a hypodermic of morphin before the administration of the chloro- form. This idea came from Claude Bernard, who reported experiments on dogs along similar lines in 1869. Another attempt to show the cause of death under chloroform was made by Lauder Brunton in 1887. He stated his theory to show that incomplete anesthesia with chloro- form was the most frequent cause of fatal results. George Foy, in 1889, supported these views. The Use of Chloroform Accompanied with Danger.^ — The Second Committee of the British Medical Association appointed to investigate the effects of anesthetics, their safety, and methods of administration, after studying reports of 36,000 cases in hospital and private practice, concluded that no method of using chloroform was free from danger. They found ether singularly safe in healthy individuals, though minor troubles more commonly resulted from its use. Their final conclusion was that the most important factor in the administration of anesthetics was the experience already acquired by the administrator. The Third Committee of the British Medical Association was ap- pointed in 1901, to put the determination of chloroform quantitatively upon a sound basis. They endeavored to discover the smallest possible dose, by volume in the atmosphere breathed, necessary to produce an- esthesia; and also the smallest possible dose necessary to maintain anesthesia after loss of consciousness. They recommended an inhaler devised by Vernon Harcourt, which permitted a maximum of 2 per cent of chloroform vapor with gradations downward. Chloroform and Oxygen. — In an attempt to make chloroform safer for anesthetic purposes, ISTeudorfer, of Vienna, introduced the use of chloroform and oxygen in 1886.^ Bertel advocated it before the St. 'His method was described in the Lon. Med. Becord, THE HISTORY OF ANESTHESIA 27 Petersburg Medical Society, as also did von Idelson. It did not gain favor because of the lack of a device for regulating proportions. Kreutz- mann, of San Francisco, in 1887, wrote a description of a simple ar- rangement for administering chloroform and oxygen. He used the Junker Inhaler and spoke very highly of the results. He commented on its greater rapidity, lack of marked excitement, quicker return to consciousness and fewer unpleasant after-effects. On January 25, 1896, the Britisli Medical Journal stated that the number of cases of the use of chloroform and oxygen were then too few for any general conclusions to be drawn. Oxygen was used with chloroform by Schall, of Brooklyn, in 1895, and Northrop, of Philadelphia, and this combination has been the routine anesthetic in a hospital of Pittsburgh for nine years. Combinations and Sequences in Anesthetics. — Among other recent advances, it may be noted that anesthetics are used more in combination and sequence than ever before. In pulmonary anesthetics, the placing of rebreathing upon a scientific basis by Gatch, and the combination of general and local anesthetics by Crile, are noteworthy advances. Por spinal and regional anesthesia, electrical, rectal, intratracheal insuiflation, morphin, and intravenous anesthesia, and hypnotism, the reader is re- ferred to the chapters dealing especially with the different forms of anesthesia. Ethyl Chlorid. — Ethyl chlorid is being used more and more where it is impossible to use nitrous oxid, on account of the diflfieulty of pro- curing the gas in tanks, etc., in certain localities. Its general properties were discovered by Carlson in 1896; in 1902, it was introduced in England as a general anesthetic, and in the latter country it has recently almost displaced nitrous oxid. Importance of Trained Anesthetists. — The tendency of the present day is toward absolute accuracy in the choice of anesthetics and in the amount administered. This, together with a competent anesthetist who has been thoroughly trained for that particular work,^ insures to the patient of the twentieth century complete oblivion from pain during surgical operations, with a minimum of discomfort and risk. BIBLIOGRAPHY "Anaesthetics Ancient and Modern ; an Historical Sketch of Anaesthesia." Burroughs, Wellcome & Co., London, 1907. Bigelow, Henry J.: "Surgical Anaesthesia, Addresses and Other Pa- pers." Boston, 1900. Buxton, Dudley W. : "Crawford Williamson Long (1815-1879), the Pioneer of Anaesthesia, and the First to Suggest and Employ Ether 1 See Chap. IX, p. 361. 28 ANESTHESIA Inhalation during Surgical Operations." Eeprinted from the Pro- ceedings of tlie Royal Society of Medicine, 1912^ 5, 19-45. Colton, J. Q. : "Anaesthesia : Who Made and Developed This Great Dis- covery ?" ■ A. G. Sherwood & Co., New York, 1886. "A True History of the Discovery of Anesthesia," A. G. Sher- wood & Co., New York, 1896. Emerson, E. W. : "A History of the Gift of Painless Surgery." Hough- ton, Mifflin & Co., Boston and New York, 1896. Foster, Burnside: "The History of the Discovery of Anesthesia." St. Paul, Minn., 1896. Foy, G. : "Anaesthetics, Ancient and Modern." London, 1889. Hayden, William E. : "History of Anesthesia, or Painless Surgery." Inter. J. Surg., New York, 1896. Hodges, Eichard Manning: "The Introduction of Sulphuric Ether," 1891. Lyman, Henry M. : "The Discovery of Anesthesia." Va. Med. Mon., Sept., 1886. McManus, James : "Notes on the History of Anesthesia." Hartford, Clark & Smith, 1894. Maduro: "The Status of General Anesthesia, in 1900." Med. News, Sept., 1900. Morton, William James : "Memoranda Eelating to the Discovery of Surgical Anesthesia," and Wm. T. G. Morton: "Eelation to This Event." New York, 1905. Nevius, Laird W. : "The Discovery of Modern Anesthesia. By Whom Was It Made? A Brief Statement of Facts." New York, 1894. Old Penn, April 6, 1912, 10, No. 19, 587. Patton, J. M. : "Anesthesia and Anesthetics." "Eeport to the House of Eepresentatives of the United States of Amer- ica, Vindicating the Eights of Charles T. Jackson to the Discovery of the Ansesthetic Effects of Ether Vapor, and Disproving the Claims of W. T. G. Morton, to That Discovery. Testimony in Eelation to the Claims of Dr. Horace Wells, with Evidence Explanatory Thereto." Washington, 1853. Eice, Nathan P. : "Trials of a Public Benefactor." New York, 1859. Shaw, S. Parsons: "Who Discovered Anesthesia?" Palmer & Howe, Manchester, 1868. Sims, James Marion : "The Discovery of Anesthesia." J. W. Ferguson & Son, Eichmond, 1877. Simpson, Sir James Young: "Anesthesia, etc." D. Appleton & Co., New York, 1872. ■ "Answer to Eeligious Objections Advanced Against the Em- ployment of Anaesthetic Agents in Midwifery and Surgery." Lon- don, 1847. THE HISTORY OF ANESTHESIA 29 Smith, Truman : "An Inquiry into the Origin of Modern Anesthesia." Hartford, Brown & Gross, 1867. "Testimony Establishing the Claim of William T. G. Morton, M.D., on the Ether Discovery." "The Semi-Centennial of Anesthesia, October 16, 1896/' Mass. Gen. Hospital, Boston, 1897, United States Congress. Senate Eeport from Select Committee, etc., 32nd Congress, 2nd Session, Eep. Com. No. 421, Feb. 19, 1853. Warren, Edward: "Some Account of the Letheon, or Who Was the Discoverer?" Dutton & Wentworth, Boston, 1847. Warren, J. Collins: "The Influence of Anesthesia on the Surgery of the Nineteenth Century," 1896. Warren, J. M. : "The History of Anesthetics from an American Point of View." Welch, William H. : "A Consideration of the Introduction of Surgi- cal Anesthesia." Young, Hugh H. : "Long, the Discoverer of Anesthesia." Johns Hop- Uns Hist. Bull., Nos. 77-78, Aug.-Sept., 1897. CHAPTEE II GENEEAL PHYSIOLOGY OF INHALATION ANESTHESIA Inteoductory Eemarks : Definition of Terms ; Chief Anesthetic Agents. Theories of tpie Action of General Anesthetics: Spencer's Theory; Binz's Theory; Bernard's Theory; Dubois' Theory; Schleich's Theory; Miiller's Theory; Meyer-Overton Theory; Wright's Theory; Traube's Theory; Mathews-Brown Theory; Moore-Eoaf Theory; Gill's Theory; Hober's Theory; Baglioni's Theory; Eeicher's Theory; Gros's Conclusions ; Burker's Theory ; Verworn's Theory ; Conclusions of Lillie ; Conclusions. Effects of Inhalation Anesthetics upon Various Parts of the Organism : The Bespiratory System ; The Circulatory System ; The Muscular System; The Glandular System; The Nervous System. Factors Which May Be Said to Modify the Physiology of Anesthesia as Ordinarily Induced: Warming the Agent; Experi- ments on Warming Ether ; Effects of Moisture ; Combining Oxygen with the Agent ; The Influence upon Anesthesia of Oxygen Intra-abdominally Administered ; Preceding the Administration with Oil of Bitter Orange Peel ; Utilizing Carbon Dioxid. INTRODUCTORY REMARKS All attempts to give a detailed account of the action of anesthetic agents in general upon the organism reveal the practical impossibility of proceeding very far without employing a modifying phrase, "this varies with the agent employed," "according to conditions," "with chlo- roform," "with ether," etc. Therefore relatively little space is given here to the general physiology, special attention being directed to the particular physiology of each agent in the individual chapters where the several drugs are discussed in detail. In fact, the special physiology of ether, chloroform, or other inhalation anesthetic agent, is of far more value to the practical anesthetist than is the physiology which is applica- ble alike to all, the former having been evolved largely from clinical ob- servation, whereas the latter is the outcome chiefly of laboratory ex- perimentation, many points concerning which have not been definitely determined. 30 GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 31 Definition of Terms. — The term "general anesthetic" is employed in contradistinction to local or spinal analgesic. The state of general an- esthesia, or unconsciousness concurrent with insensibility to pain, is usually brought about by inhalation, but may be induced by various agencies introduced into the organism by other channels than the respiratory system. It may perhaps also be induced by hypnotism and electrical influences. The various narcotic and analgesic drugs which are administered by mouth or otherwise are excluded from discussion in this chapter. The state induced by the administration of inhalation anesthetics is designated, by the usually accepted phraseology, general anesthesia, anesthesia, and narcosis, all signifying unconsciousness with general loss of sensation, including, of course, loss of pain sense. Analgesia, loss of sensibility to pain, is not to be confounded with the above terms. The terms "light anesthesia" and "heavy anesthesia," whose use has been challenged by some writers ^ are not in- correct, if considered to apply merely to degrees or stages of anes- thesia. Certain factors are generally accepted as entering into the physico- chemical relations of the anesthetic agent to the organism, giving rise to results which may be noted and controlled clinically. These factors are as follows: (1) It should be of such nature or combination, or must be capable of such methods of administration, as will reduce the danger to life to a minimum. (2) The anesthetic agent should possess such physical properties that it is easily taken into the system. (3) It should produce the general, complete, or temporary inhibi- tion of action of the nervous mechanism presiding over cerebration, sensation, and motion, (4) It should be capable of administration with the least inter- ference with respiration, circulation, or other vital processes. (5) It should act in such manner that its immediate effects are at all times under the control of the administrator. (6) It should reduce general shock to a minimum. (7) It should not cause serious or lasting after-effects, the organism promptly resuming the physiological functions existent immediately before the administration of the anesthetic. In the light of recent laboratory and clinical experiments, a further requirement may be added to those heretofore generally accepted as applying to the satisfactory inhalation anesthetic ; this is : (8) The agent should be of such a nature or combination as to render possible the practically complete elimination of the second stage of an- '"Eeview of Blumfeld's Treatise," Lancet, Sept. 21, 1912. 32 ANESTHESIA esthesia — the stage of excitement — during which the dangerous phe- nomena of anesthesia are often noted. Chief Anesthetic Agents. — The chief agents and combinations of agents which fulfil the above requirements are: (1) nitrous oxid; (2) ether; (3) ethyl chlorid; (4) chloroform; (5) combinations and se- quences of the above with each other and with oxygen. THEORIES OF THE ACTION OF GENERAL ANESTHETICS Inasmuch as there are still "mysteries of anesthesia/' many points of physiology upon which expert opinions differ, we present a brief review of the theories concerning the mode of action of anesthetics, as ad- vanced by the earlier investigators as well as by more recent writers. No attempt has been made to catalogue all the theories proposed, or to follow strict chronological sequence. Spencer's Theory.^ — Narcotic and anesthetic agents are commonly supposed to have special relations to the nervous tissue, rather than to other tissues. Because of the different effects produced, it is even sup- posed that some of them have elective affinities for the matter composing certain nervous centers rather than for that composing others. As the same anesthetic does not act in the same way on all persons, but here affects one center more, and there another, it must be assumed that the chemical compositions of these centers are in such cases interchanged. Since, in the same individual, the same quantity of the same anesthetic will produce quite different effects in different states of the circulation, the hypothesis requires the supposition that these contrasts of chemical composition among the nervous centers interchange from hour to hour. The various substances that affect the nervous system — the narcotic and anesthetic agents — are substances that produce changes in albumi- nous matters, their respective effects being modified by the various con- ditions under which they act. "Agents having powerful- affinities for components of the tissues and fluids,'' according to Spencer, "given in small quantities to avoid destruction of the membranes, can scarcely reach the nervous system in uncombined states; and may be expected to work their respective effects through the instrumentalities of the com- pounds they have formed. The most conspicuous effects will be wrought by those agents which, while they can produce molecular changes in albuminous substances, have not such powerful affinities for them, or for their elements, as to be arrested on their way to the nervous system. The anesthetics and narcotics may fairly be regarded as fulfilling this requirement." It need not be supposed that the anesthetic or narcotic has more affinity for protein-substance of nerve corpuscle or nerve fiber ^ Spencer, Herbert : * ' Synthetic Philosophy, ' ' Vol. I ; " Principles of Psychol- ogy, " Appendix; "On the Actions of Anaesthetics and Narcotics," 631. GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 33 than for the other forms of protein-substance with wliich it coinos in contact. Its effect is comprehensible, however, as resulting from the structural relations of nerve corpuscle and nerve fiber. In order to understand why excitement precedes narcosis, one must observe the different relations of nerve corpuscle and nerve fiber to the blood. The vesicular tissue of the nervous system is far more vascular than its fibrous tissue. While the matter of the nerve vesicles is so arranged as to offer the least possible obstacle to the reception of the fluid from the adjacent capillaries, the matter of nerve fibers is shielded by a medullary sheath. When any agent, therefore, which is capal^le of so changing the molecular state of nerve matter as to arrest its function is carried into the blood, the first action is upon the nerve corpuscles. "Each change produced in one of these," according to Spencer, "implies a disengagement of molecular motion that is immediately propagated along the connected nerve fibers, and excites the parts to which they run. Every nerve corpuscle being thus quickly, acted upon, and emitting successive discharges as the successive molecular transformations are wrought in it, there results a general exaltation of state, physically in the invigorated pulse and contractions of the muscles, and as shown psychically in the rush of vivid ideas and intensified feelings." While this is going on, while some molecules of the anesthetic agent have thus quickly passed from the closely adjacent capillaries into the almost naked matter of the nerve corpuscles, other such molecules are elsewhere on their way through the outer coats of the nerve tubes and the medul- lary sheaths within these, reaching, in time, the bundles of fibrillse forming the axis-cylinders. The isomeric changes which they immedi- ately begin to produce in these at first add to the general excitement. As the anesthetic invades a nerve fiber more and more, a greater and greater number of its molecules are rendered unable to transfer a wave of the peculiar isomeric change which constitutes a nervous discharge, and finally the fiber becomes impermeable. The impermeability, other things being equal, takes place sooner in the longer nerve fibers than in the shorter, the probability being that, after a given interval, a long fiber is more likely than a short fiber to be invaded at some parts of its course. This presumably ex- plains why, in an animal, anesthesia occurs first in the hinder extremi- ties, the parts of the surface nearer to the nervous centers losing their sensibility later. ISTumerous factors (point of absorption; rapidity of absorption; quantity absorbed ; relative molecular mobility of the agent ; its chemical relation to the blood and other substances; general state of circulation and of circulation in each nervous center; and character of nerve fibers acted upon) cooperate to cause variation in the effects produced by the various agents, by different doses and by the same dose under different 34 ANESTHESIA conditions. It is not necessary, therefore, to assign elective affinities for special centers as the only possible causes of the special effects. Binz's Theory/ — The ganglion cell, according to Binz, is the point of attack of the anesthetic agent. In his experiments, fresh sections of the brain cortex of rabbits were placed in a one per cent solution of morphin hydrochlorid, or exposed to chlorin vapors. The effect of coagulation-necrosis was produced, as is seen when protoplasmic poisons of neutral reaction are allowed to act upon large transparent infusoria. The protoplasm is at first darkened, and the movements become slug- gish; later on the protoplasm becomes granulated, and the movements cease. Eecuperation may take place from the first stage, by washing away the poisons, but not from the last stage. The first stage is likened by Binz to the sleep of the cell; the last to death. The first trace of coagulation may redissolve but coagulation itself does not. Bernard's Theory.^ — Bernard regarded the ganglion cell as the point of attack of the narcotic agent. In his opinion, the mechanism of an- esthesia is always the same, in spite of the difference of the narcotic agent; for they all produce one identical modification in the ganglion cell. This modification of the ganglion cell consists in a semi-coagula- tion of^ the protoplasm of the nerve-cell, this semi-coagulation being merely transitory, the protoplasm resuming its previous state after the removal of the narcotic agent from the cell. This view was derived from the rigidity of muscle fibers after their exposure to chlorin vapors. Miiller ^ points out that the same mechanism cannot be assumed to underlie all narcoses, the mechanism of indifferent narcotics differing from the mechanism of narcosis caused by many basic narcotics. He believes, however, that a semi-coagulation of the protoplasm is pro- duced hy the majority of the basic narcotics. Dubois' Theory.* — Dubois proposed a modification of Bernard's theory, holding that narcotics act hy producing a dehydration of the protoplasm, or by decreasing the dissociation of the inMhition-water of the tissues. Organisms which are exposed to the action of these dehydrating substances are transformed into a state of latent vitality. Miiller ^ points out that this theory is entirely erroneous, the water that is withdrawn being derived from the "cell juice," but not from the protoplasm. Eichet states that a compound becomes a more efficient ^Binz, C: " Ueber Anaesthetika, " Deutsche Klinik, 1860, No. 29, 277; "Ozonisierte Luft, ein schlafmachendes Gas," Berl. Min. Wochnschr., 1882, No. 1, 6; "Die Wirkung ozonisierter Luft auf das Gehirn, " Berl. Iclin. Wochnschr., 1884, No. 40, 633. ^Bernard, C: " L 'anesthesie, " Union med., Paris, 1869, 8, 109. 'Miiller, B.: " Narkologie, " 7. "Dubois, E. : "Contribution a I'etude de la physiologie generale des anes- thesiques," Seances et Mem. Soc. de Biol., Oct. 24, 1885, 625. ° Miiller : Loc. cit. GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 35 narcotic, or a stronger poison, the slighter its solubility in water. This assertion applies to a definite number of narcotics, up to a certain de- gree. All indifferent narcotics, of difficult solubility in water, have the property of penetrating quickly to the entire protoplasm and require only a few seconds to get into the cell juice. Overton's statement holds good, that the strongest narcotics are those compounds which at the same time combine a very slight solubility in water with a very great solubility in ether, olive oil, or the lecithin mixtures. Schleich's Theory.^ — According to Schleich, the first influence of the anesthetic agent is manifested hy the stimulation of peripheral organs, followed hy local stimulation at the end apparatus of the sense-organs. The effects upon the central apparatus are as follows : The blood circulates in the neuroglia in very fine vessels, and the first effect of the narcotic is felt as a heavy, dull sensation over the entire head; the result of the neuroglia irritation would be sleep, if the ganglion cells were not themselves stimulated at about the same time. As a matter of fact, this sleep can be produced in the early stage in certain individuals, for example in children, by very gradual an- esthetization. The small quantities of the anesthetic which at first cir- culate in the blood may cause a stimulation of the vasomotors, and thereby a narrowing of the vessels, on account of the close connection of the neuroglia protoplasm cells with the vessels. The function of the protoplasm cells is thereby diminished, due to limited fluid; the inhi- bition is lessened; ideas and thoughts travel about unchecked. It is not until the onset of vasomotor paralysis that the vessels become larger, so that the narcotic agent can stimulate the protoplasm cells directly. The roaming ideas are now restricted. The inhibitory function of the neuroglia advances and penetrates between the individual sensory asso- ciations. The situation becomes blurred; momentary consciousness is lost; only individual ideas reach consciousness; the condition takes on more and more similarity to sleep, at first restless and full of dreams, later on deep and quiet. The pupils are still sensitive to light stimuli, but no longer reach their full width on closure of the lids ; the contrac- tion increases as the narcosis advances. The pupils are contracted also in sleep. There probably exists a reflex arc between neuroglia irrita- tion and oculomotor function, or sympathetic paralysis, respectively. Poisons such as chloroform are relatively mild, because they are first accompanied by neuroglia irritation, whereas the true cell poisons penetrate at once into the ganglion cells, exerting their relative influence beyond the protective action of the neuroglia, and acting upon the gan- glion cells by way of the lymph spaces and blood vessels. Narcoses with chloroform, ether, alcohol, etc., are increased physiological mechanisms, namely, changes in repletion with blood and irritations of the neuroglia. 'Schleich: "Zur Infiltrations Anaesthesie, " Therap. Monatsh., 1894, 429. 36 ANESTHESIA When these substances are administered in definite quantities which create a state of equilibrium between the action of the narcotic and the power of resistance of the neuroglia, their effect becomes narcotic, and this effect increases the more the scale of equilibrium tips toward the narcotic, until finally the neuroglia is overcome, and the effect is then the same as that of the cell poisons which directly attack the ganglion cell, omitting the neuroglia. Schleich considers the narcotic agents as primary neuroglia poisons, and their antagonists (the cell poisons) as primary cell poisons. He also assumes a variable sensitiveness of the neuroglia in the different developmental stages. The effect of chloroform, and the majority of narcotics, upon the individual centers of the human brain, pursues a course in inverse ratio to the phylogenetic development of the centers. The extraordinarily poisonous effect of chloroform and of morphin upon certain individuals is explained by him as due to the fact that, in these cases, the neuroglia does not react to the ordinary toxic dose by a stimulation, but directly by paralysis. Miiller's Theory.^ — After considering various theories of narcosis, Miiller formulated his own view concerning the mechanism of anesthesia. After the narcotic agent has reached the ganglion cells of the cere- bral cortex, it exerts its actiofi upon tlie lecithin-cliolesterin mixture of the ganglion cell, causing it to undergo a physical transformation. Ac- cording to Schleich's theory, the plasma cells of the neuroglia are also important and possess inhibitory properties; they surround each func- tionating ganglion cell and communicate directly with a vessel. As the plasma cells are directly connected with the perivascular lymph spaces of the vessels, and are themselves surrounded by lymph spaces, the narcotic agent which is contained in a definite concentration in the blood plasm must be taken up by the lymph of the lymph spaces, and an equilibrium in the concentration of the two fluids in the narcotic must become established. It depends upon the composition of the proto- plasm of the plasma cells, how much narcotic they will take up before this reaches the ganglion cell. The paralysis of the plasma cell rep- resents that instant at which the quantity of the narcotic in the plasma cell is such that no additional amount can be taken up. The narcotic, at this moment, gets also into the ganglion cell. The plasma cell is now passed without its protoplasm taking up anything of the narcotic, and the ganglion cell takes up the narcotic from the intercellular lymph. The function of the neuroglia explains the different effects of the nar- cotic upon the individual centers. By assuming the presence of lecithin- cholesterin mixtures also in the plasma cells, it becomes intelligible that they possess the capacity of dissolving the narcotic agents. Possibly, ^ Miiller, B. : Loc. cit. GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 37 these plasma cells contain still anotlicr similar substance, which floes not exist in the ganglion cells, and tlioi-cby invests the plasma cells with the capacity of fixing still larger qiiaiitiiies of the narcotic. This other body may be contained in larger amounts in the phylogencti(;ally older plasma cells than in the younger cells, thus accounting for tlie prolonged resistance in still another way. The significance of the solubility of the narcotic in the cells of the neuroglia is at once evident, when the function of the neuroglia is interpreted as something more than connective tissue function. The different efi^ect upon the ganglion cells is explained by the different niimber of existing plasma cells. The action of the neuroglia consists in modifying the solubility of the nar- cotic agent and thereby controlling the rate of its penetration into the ganglion cells. Meyer-Overton Theory. — In 189 C Hans Meyer announced his theory of narcosis ; ^ the following year E. Overton described his theory of anes- thesia;^ and in 1905 Meyer restated his theory. -"^ Since these two theories were formulated independently and without conference,* and in general agree, this explanation of anesthesia is usually referred to as the Meyer-Overton theory. According to Meyer, the narcotizing substance enters into a loose physico-cliemical combination ivith the vitally im.portant lipoids of tlie cell, perhaps with lecithin, and in so doing changes their normal rela- tionship to the other cell constituents, through ivhich an inhibition of the entire cell chemism results. The narcosis disappears as soon as the loose, reversible combination, dependent upon the solution tension, breaks up. In accordance with these views Meyer formulated the following statements : "(1) All primarily indifferent chemical substances which are solvents for fat and substances resembling fat must exert a narcotic action upon living protoplasm, in so far as they can diffuse therein. "(2) The effect must manifest itself first, and most strongly, in those cells in whose chemical structure these fatty or lipoid substances pre- dominate and presumably are the essential carriers of the cell function, — namely, in the first place, in the nerve cells. "(3) The relative efficiency of such narcotic agents must be de- pendent upon their mechanical affinity for lipoid substances, on the one hand, and for the remaining body constituents, i. e., princijjally ^ArcMv f. exper. PatJiol. u. Pharmakol., May 16, 1899, 110, 119. " ' ' Studien iiber die Narkose, zugleich ein Beitriig zur allgemeiuen Phar- makologie, " Jena, 1901. ^ ' ' The Theory of Narcosis, ' ' Harvey Lectures, 1905, 1 ; J. Am. Med. Assn., Jan. 20, 1906, 167. *J. Am. Med. Assn., Jan. 29, 1906, 169. 38 ANESTHESIA water, on the other hand. It is dependent, therefore, upon the division coefficient which determines their distribution in a mixture of water and lipoid substances." Overton carried out extensive observations and investigations con- cerning the osmotic properties of living plant cells and animal cells, followed by experimentation with general anesthesia. He was firmly convinced of the fact that the mode of action of anesthetic agents can in no way be explained on the basis of chemical reaction ; for the reason that many of the strongest indifferent narcotics belong chemically to the most stable and sluggish compounds. The effect of narcotic agents is essentially a function of their lipoid solubility. Overton showed that substances may be divided into different groups according to the rapidity with which they diffuse into protoplasm, the rate of diffusion, as a general rule, depending upon the solubility of the substances in fat, lecithin, and lipoid substances of that type. If Sr represents the solubility of the substance in fat, and S^ that of o the same substance in water, then the ratio — ^ is termed the distri- bution coefficient of the substance. According to Overton, the value of this coefficient determines the velocity of diffusion into cell protoplasm. It has been indicated by Meyer and Overton^ that anesthetics and narcotics are usually substances which diffuse rapidly, and that, there- fore, these substances should have a high distribution coefficient. Meyer accordingly compared the aliphatic narcotics, and found that the nar- cotic power of these was roughly proportional to the magnitude of the distribution coefficient. This finding has been expressed as follows: The strength of the narcotic action of a compound is dependent upon its solubility in lipoid substance.^ But, as has been pointed out by May,^ this is not exactly correct, since it depends not so much on its actual solubility in lipoid substances as upon the ratio of its solubility in lipoids to that of its solubility in water." Meyer compared the narcotic power of the aliphatic narcotics by ascertaining the smallest concentration which would produce a definite physiological effect, and he expressed the values as fractions of a normal solution, calling these the "liminal values." He and Baum* discussed the work of Dubois ^ in reference to which they advanced the theory that the relative strengths of anesthetics are dependent upon their mechan- ical affinity for fatty substances, like lecithin in the protoplasm, on the one hand, and to the other constituents in the protoplasm, especially ^ Arch. f. exp. Path. u. Pharm., 1901, 42, 109 and 119. ^ See Hober's Theory, p. 46. ^ Loc. cit. * Arch. f. exp. Path. u. Pharm. 42, 109. *See Dubois' Theory, p. 34. GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 39 water, on the other hand. In support of these views, they showed that the proportion between solubility in fat and solubility in water of a number of narcotics runs parallel with their anesthetizing activity. The theory of Overton and Meyer is well supported by the paral- lelism of narcotic effect and distribution coefficient. Then, too, a num- ber of subsidiary facts appear to lend it additional support ; for example, the observation of Mansfield,^ that some narcotics have a more powerful action when administered to starved animals, the explanation suggested being that in these there is less tissue fat to absorb some of the narcotic and that a greater portion of the latter is in consequence absorbed by the central nervous system; and the observation of Tunnicliffe and Eosenheim - that the addition of lecithin protracts the effect of chloro- form on the heart. ^ However, other facts seem to show that the theory is, to say the least, incomplete. For instance, the peripheral nerves contain a large amount of lipoid substance, yet they are much less affected by the ali- phatic narcotics. It has also been pointed out by Cushny * that inany aromatic compounds have a high distribution coefficient, but are never- theless devoid of narcotic action. There is, however, a possible expla- nation of these facts in Traube's theory (see p. 48) of surface tension. It appears reasonable to conclude from these facts : (1) That the rapid penetration of the cells should be the most essentia! condition of enabling a substance to exert its effect on the interior of the cells. (2) That, after the substance has gained entrance, its solubility in the cell lipoids may be the important factor in determining narcotic action. The Meyer-Overton theory is more than merely interesting. It ostensibly gives a simple explanation of narcosis and seems to afford a means of elucidating other processes, as phagocytosis.^ In support of the combination of, say, chloroform with lecithin, we have the analogous conduct of this compound with salicylid," leprarin,^ and even water ; ^ and further support is given to the Meyer-Overton theory l)y the finding ^Cetitr. Physiol., 20, 664. ^ Froc. Physiol. Soc, 1903, 15. ^ Tunnicliffe and Eosenheim studied the action of chloroform and ether on the heart by adding them to saline fluid perfused through the heart by Locke's method. The depressing action on the heart produced by chloroform was found to be very marked, but if lecithin was also added the effect was found to be delayed. * Cushny: "Text-book of Pharmacology," 1904, 128. = See Graham: J. Am. Med. Assn., March 26,, 1910, 1044. ''Anschiitz: Ann., 273, 94. 'Kassner: Arch. Pharm., 237, 44. *See Z. anal. Chem., 25, 118. 40 ANESTHESIA of Nerking/ that, in the case of animals to which a solution of lecithin has heen administered, the anesthesia lasted for "a much shorter time" than in the case of the control animals, and the work of Graham,^ who found that lecithin and olive oil added to etherized blood restored phagocytosis. Although the theory is well supported by certain evidence, it is too specific to be altogether satisfactory. There is much uncertainty as to the mode of action of anesthetics and particularly as to their effect upon permeability. While some writers hold that anesthetics increase permeability, others take the opposite view.^ As pointed out by Osterhout,* to clear up this confusion appears to be a necessary step toward a theory of anesthesia. He seems to have attained a definite solution of the problem in the cases he describes — a result due to the employment of quantitative methods. The experiments of Osterhout were made by measuring the con- ductance of living tissues of a marine plant, laminaria. Under the con- ditions of the experiment, an increase or decrease of conductance signified a corresponding increase or decrease of permeability.^ The anesthetics (ethyl ether, chloroform, chloral hydrate, and alcohol) were mixed with sea water and sufficient concentrated sea water was then added to make the conductivity equal to that of sea water. The material was then placed in the mixture and its conductance was measured at frequent intervals. Two distinct effects were observable in the experiments conducted by Osterhout. One was a toxic effect evidenced by an increase in permeability, while the other involved a decrease in permeability. He was forced to the conclusion, from the results obtained, that it was the reversible change, involving a decrease of permeability, which was associated with the anesthetic action. This is indeed reasonable.'' Os- terhout pointed out that the fact that typical anesthetics decrease the permeability of the tissue to ions is significant in view of the fact that the transmission of nervous and other stimuli is believed to depend on the movement of ions within the tissues. Wright's Theory.'' — Wright undertook an investigation to determine ^Miinch. med. Wocli., 1908, 1733. -J. Am. Med. Assn., March 20, 1910, 1043. =*Cf. Hober: " Physikalische Chemie der Zelle und der Gewebe," 1911, 219, 223, 489; Lillie: Am. J. Physiol, 1912, ^9, 372; 30, 1; and Lepeschkin: Ber. d. hot. Ges., 1911, S9, 349. * Science, n. s., 37, No. 942, 111. ■"The method is described in Science, n. s., S5, 112 (1912). " The distinctive mark of an anesthetic is the reversibility of its action ; hence it can hardly be concluded that this action is associated with an irre- versible change in permeability. Such a change is not peculiar to anesthetics, although common to all toxic substances. ' Wright, Hamilton : ' ' The Action of Ether and Chloroform on the Neurons of Rabbits and Dogs," J. Physiol, 1900-1, 26, 30, 362. GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 41 whether chloroform and ctlicr produce any transient or permanent changes in the cortical or spinal neurons. In rabbits he found that these agents produced changes in the nerve cells of both the brain and spinal cord. These changes were slight at first, but became more marked as the anesthesia continued. The principal change was described by him as "rarefaction." In the advanced cases he employed the term "skeleton cell," and, in the most marked cases, he found that a "pseudo-degenerative" change had set in. In dogs there were practically no changes up to two hours, but, between that time and tour hours, changes occurred in the nerve cells similar in kind to those observed in rabbits, although less in degree. These changes became more marked as the anesthetic was continued. Wright regarded the changes observed in the cells and their pro- cesses as due directly to the influence of the anesthetic, and not due indi- rectly to the capillary anemia which is produced. Inasmuch as it is generally conceded that ether and chloroform cir- culate in the blood as such, producing no biochemical changes in the blood, Wright concluded that the neuronal changes are hiocheraical in nature, and are 'produced by the anesthetic that readies them via the blood stream. There is nothing, he holds, to suggest that chloroform or ether could cause these changes mechanically; the supposition that they act chem- ically is extremely probable. It is obviously impossible to say that these changes occur in human beings. Wright did not consider, however, that there is any analogy between the changes described and those biochemical anabolic and katabolic changes that occur in daily life, and mark sleeping and waking hours. He regarded the action of narcotics, such as ether and chloro- form, as pathological, not very intensely so, yet as something which is remote from physiological processes. In sleep there is probably an opportunity, he says, for the constituents of the nerve cells to undergo anabolic changes, whereas in the unconsciousness produced by anes- thetics the process appears to be associated with an exhaustion of them. A subsequent series of experiments^ was undertaken (1) to determine whether a still more prolonged period of anesthesia renders the changes more intense, and (2) to ascertain whether the pseudo-degenerative change is permanent: the answer to the first question was affirmative; to the second, negative. In the cases in which the anesthesia was kept up longest it was found that even the nuclei and the nucleoli were afl^ected, the latter being the last part of the cell to show the effect of the drugs. The slow return of the conjunctival reflex in these cases, he thought, indi- cated that after a certain period of anesthesia (six hours in the dog) ^Wright: /feid., page 363. 42 ANESTHESIA the depression of neuronal function becomes more rapidly profound, and that there is a limit to the time of safe anesthesia. The histological changes observed induced this view. A greater alteration occurred in the cells during the three hours between the sixth and the ninth hours of anesthesia than during the five hours between the first and the sixth hours. The changes observed in the cells were transitory, disappearing with the disappearance of the drugs from the circulation and tissues, or soon thereafter. Forty-eight hours after nine hours of ether narcosis the cells were found to be practically 'normal. The rarefaction of the cell substance and the formation of monili- form (necklace-like) swelling noted in the dendrons, according to Wright, may modify nervous function. "To such changes," he says, "may perhaps be attributed those losses of memory, slight manias and melancholias that are now and then reported to follow prolonged anes- thesia in the human subject.^' Traube's Theory.^ — In his theory of the production of general anes- thesia, Traube contradicts the lipoid solubility, claimed by Overton, as the primary cause of the penetration of the anesthetic agent into the cell. This cause, according to Traube, consists in the surface ten- sion. When two fluids of different surface tension are separated through a membrane, the fluid having the lower tension can find its way to that Avith the higher tension; so that the difference between the surface tensions explains the entrance of the anesthetizing fluid into the cells.- He also claims the existence of a close conformity between the narcotic efficiency and the surface tension in the case of 'pure anesthetic agents which are free from toxic side-effects. Mathews-Brown Theory. — Mathews ^ made Nef's bivalent carbon hypothesis * the basis of a hypothesis for protoplasmic respiration which ^Traube: "Theorie der Osmose und Narkose, " Arch. ges. Physiol., 1904, 105, 451; Phil. Mag. (6), 8, 704; Z. physiol. Chem., JOS, 541. - When the drug has thus gained entrance to the cell, it may exercise its narcotic power in proportion to its solubility in the cell lipoids. ^ Mathews, A. P. : Biol. Bull, 1905, 8, 331. * The bivalent carbon hypothesis of Nef (J. Am. Chem. Soc, 26, 1549) ap- proaches the action of narcotic agents to the fundamental reactions of organic chemistry. According to his investigations of the chemistry of the element car- bon, protoplasmic respiration can be explained as a vital reaction through the decomposition of water, on the basis of a change in valence of the carbon atom from four to two. The quadrivalence of carbon is not constant, the existence of carbon compounds containing bivalent carbon having been definitely estab- lished. The bivalent carbon compound of cells, or their respiratory elements, are the point of attack of the entering anesthetic agent. The action is assisted by a rise in temperature. Substances which are perfectly indifferent chemi- cally, such as the volatile saturated hydrocarbons, may produce anesthesia by entering into a loose chemico-physical combination with certain cell constituents. GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 43 Brown ^ considers plausible. The bivalent carbon compound of the pro- toplasm, luliich, according to Mathews, may be either simple or complex, decomposes the water of the tissues into its elements. The oxygen, com- bining ivith the compounds constituting protoplasm, oxidizes them. The hydrogen, uniting with free oxygen or other substance in the tissues, passes off as gas. Mathews holds that anesthetics inhibit the action of the bivalent carbon, thereby decreasing the respiration of the cell protoplasm, result- ing in the stage known as anesthesia. Brown, referring to this theory, thought it more likely that the sub- stances producing a narcosis do so, "not by an action on any one of the essential processes of the protoplasm, but from the combined influence of all of them. The role that the lipoids of the cell play in narcosis may be only that of a solvent or gatherer for the narcotic, or more, depending upon whether or not the lipoid is concerned with the essential living processes of the cell." Mathews had previously called Brown's attention to the fact that starfish eggs were greatly affected by chloroform, ether, etc. The efl'ect appeared to be a partial liquefaction of the protoplasm. Mathews sug- gested that possibly the power of each member of this group of com- pounds to liquefy the starfish eggs might be proportional to its narcotic power. Mathews had made some experiments along this line, a report of which was published. This work was repeated and extended by Brown, who made a comparative study of a number of the compounds in common use as anesthetics, narcotics and hypnotics. The change produced in the eggs was found to be a profound one. The eggs enlarged and became lighter in color; the protoplasm became less granular, and finally there was a rupture of the envelope at some spot, the contents flowing out. Brown called attention, in this connection, to Hermann's ^ observa- tion of a similar change in red blood corpuscles when treated with an- esthetics. The process indicated that the contents of the cell had been increased, in amount and fluidity. The explanation, according to Brown, seems to be that the narcotics are taken up by the fat-like bodies of the egg. From his comparative studies Brown concluded, in part, as follows : "(1) That anesthetics and narcotics, at certain concentrations, cause a profound change in the eggs of starfish. This change appears to be a the effect disappearing as soon as this loose reversible combination ceases. From this point of view, narcosis represents an inhibition of the entire chemism of the nerve cell, through changes in the normal mutual relations of the cell constituents. ^ Brown, Orville Harry : "A Pharmacological Study of Anesthetics and Narcotics," Am. J. Physiol, 1905-6, 15, 85. =" Hermann: Arch. Anat. Physiol., Wes. Med., 1866, 27. 44 ANESTHESIA partial liquefaction. The power of the compounds in bringing this about is indicative of their power as narcotics; i. e., the narcotic substance which produces liquefaction of the eggs in a dilute solution will also, in small amounts, produce narcosis. "(2) That anesthetics and narcotics do not cause the liquefaction if they are sufficiently concentrated or sufficiently diluted. The concen- trated solution causes a change which has the appearance of a coagu- lation. "(3) The most important role of the lipoids in bringing about anes- thesia probably is one of accumulation. If they are concerned with the essential process of the cell, then their part is most likely a broader one. "(4) Anesthesia is very possibly the result of an inhibition, by the compounds, of the enzymotic processes of the cell, as suggested by ISTeilson and Terry.^ "(5) Mathews' idea that the anesthetics produce their results by their influence upon the respiratory elements — the bivalent carbon compound — of the cell is a tenable one. "(6) Nef's bivalent carbon hypothesis may help to explain the more rapid narcosis when the temperature is slightly raised." Moore-Roaf Theory.- — Moore and Eoaf have found that the action of the numerous substances used as anesthetics probably depends on the general type of interaction between it and the cell protoplasm. In regard to chloroform, they pointed out that attention was not restricted to the action on nervous structures, since all cells (bacteria, amebse, ciliated cells, etc.) are equally affected. It was therefore concluded that the action must take place with some chemical constituent present in all varieties of protoplasm, and that theories based on the high con- tent of nerve cells in lecithin and fatty constituents may be disregarded. Proteid is the substance of all others universally present in all cells, and Moore and Eoaf found that chloroform formed loose compounds with many proteids ; in fact, that it would precipitate them if in excess.^ This, they thought, explains the greater solubility of chloroform in the blood, or in serum and hemoglobin solutions, than in water or in saline solutions. Their theory of narcosis may thus be expressed: The loose com- pound of proteid-cMoroform is similar to oxyhemoglobin. When anes- thesia occurs, the proteid-cliloroform compound of the blood has parted with its chloroform to the cell proteids; the compound here formed undergoes dissociation when the chloroform pressure is reduced on ^JMeilson and Terry: Am. J. Physiol., 1905, 14, 248. ' Moore and Eoaf : Proc. Boy. Soc, 73, 382. ^ Formanek (Z. pliysiol, CJiem., 29, 416) has also found that both chloroform and chloral hydrate are good precipitants of the blood pigment, particularly at 56° C. He recognized that chloroform is a precipitant for proteids. GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 45 cessation of administering the aneslhelic, and anesthesia tlius ceases. Later, Moore and Eoaf ^ supplied confirmation to the theory that chloroform and other anesthetics form unstable compounds with pro- teids, and that they produce their effects by thus interfering with the chemical activities of protoplasm. They learned that the solubility of the anesthetic was greater in serum than in water, and that beyond a certain concentration, which was definite for each anesthetic, precipi- tation of the compound with proteid occurred. It was found that the vapor pressure was always higher in an aqueous solution than in solu- tions which contained j)roteid, and determinations of freezing points and electrical conductivity supported the main contention of the inves- tigators.^ Edie ^ investigated the proteids of serum and hemoglobin in ref- erence to the work of Moore and Eoaf. It was found that the compound of chloroform and hemoglobin was less stable than carboxy-hemoglobin, and that when sufficient chloroform was added to produce precipitation the amount of chloroform found in the precipitate was constant. In the case of the serum proteids, also, the amount of chloroform was found to be fairly constant. The action of chloroform and hemoglobin has also been studied by Kriiger,* whose experiments showed that chloroform was not an indif- ferent reagent toward hemoglobin, but that it changed it into a more insoluble modification without apparently producing any profound chemical alteration. The following determined facts seem to lend the theory of Moore and Eoaf additional support: ( 1 ) It has been shown by Carlson and Luckhardt ^ that during chloroform or ether anesthesia the osmotic concentration of the blood rises. This varies with the depth, and not with the duration, of the anesthesia. The main factor in this observation ap]3ears to be that the ether or chloroform itself is dissolved in the blood, although there are other factors which cannot be altogether excluded. (2) Camus and Nicloux '' have found that ethyl chlorid is taken up by the blood with great rapidity and is also eliminated with rapidity. (3) Livon ^ found that during anesthesia produced in dogs by amy- ' Moore and Eoaf: Proc. Eoy. Soc, B., 77, 86. '■'Thompson, Yates, and Johnston, Lah. Report, Liverpool, 1905-6, 151-94; and ef. the investigations of Buglia and Simon: Arch. ital. hiol., 48, 1. " Thompson, Yates, and Johnston, Lah. Beport, Liverpool, 1905, 6, 195. *Beitr. chem. Physiol. Path., 3, 67. Cf. Gianasso: Eiforma Medica, 22 No. 19, who is of the opinion that chloroform destroys the red corpuscles of the blood. ^ Compt. rend. Soc. hiol., 55, 143. " Ihid., 145, 1437. ' lUd., 55, 143. 46 ANESTHESIA lene there is no arrest of internal combustion; but;, on extracting the blood gases, amylene was found as a constituent. Gill's Theory.^— Gill's observations concerned chloroform, which, ac- cording to his theory, abstracts oxygen from the blood, being itself destroyed in the process. "The deoxygenation factor," according to Gill, "which is their proximate cause, thus intermediates between the indirect phenomena and their ultimate cause, which is chloroform." The relation between chloroform and the blood is held by him to be twofold. It causes deoxygenation by the diminishment of the normal supply of air to the alveoli of the lungs, and by its physiologico-chem- ical action it is indirectly the cause of the suspension of the functions of the cerebral centers. Hober's Theory.^ — In his studies on the physical chemistry of excita- tion (of muscle) and of narcosis, Hober found that isotonic solutions of normal salts of the alkali metals produce currents of rest of varying intensity and direction when applied locally to the non-injured sartorius muscle of the frog. When arranged according to their power of pro- ducing this current, the various anions and cations form two series, which coincide with those which have been deduced from their action on the solubility of egg-white and of lecithin.^ This coincidence is one of the reasons for Hober's conclusion that excitation and the electrical reaction accompanying it are closely connected with the consistency of the muscle colloids. According to Hober, narcotics inhibit the change in the colloids (of the axis cylinder), which change accompanies the normal current of action, and, in accordance with the current theory of narcosis, due to Meyer and Overton, this colloidal change is supposed to occur in the lecithin. Narcosis would therefore consist, first, in the accumulation of the lipoid-soluble narcotic in the lipoid substance (lecithin), and, second, in the inhibition of the colloidal changes which excitation nor- mally produces in this substance. Baglioni's Theory.* — Baglioni maintains that narcotic effect depends ^Gill, Eichard: "The CHCI3 Problems," 1906, 2, Physiological Action. "Pfliiger's Archiv, 1907, ISO, 492; /. Chem. Soc, 94, ii, 121. ^ An examination of the effect of normal salts on the precipitation of egg- albumen, serum-albumin, and lecithin, and on the catalysis of methyl and ethyl acetates by acid and by alkali, was made by Hober (Beitr. chem. Physiol. Path., 11, 35). The results obtained by catalysis were quite regular; for instance, the chlorids of the alkali metals accelerated the acid catalysis in the order of their atomic weights, lithium chlorid being most, and caesium chlorid least, active. In neutral solutions, the order of efficiency as precipitants became irregular, and depended simultaneously on both ions. On the efficiency of various salts of the alkali metals as lecithin precipitants, see also Porges and Neubauer: Biochem, Z., 7, 152. * Francis and Fortescue-Brickdale : "The Chemical Basis of Pharmacology," 1908, 86. GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 47 on the deprivation of oxygen from the "inogen" compounds in the central nervous system; narcosis is a reducing process. This theory is based on the fact that, in the case of various groups of benzenephenol derivatives, the paralyzing action of the substance is inversely propor- tional to the amount of oxygen already in the side-chain, and that deprivation of oxygen by breathing inert gases, as carbon dioxid or hydrogen, produces symptoms similar to those of chloroform. Support to the view is had from the work of Herter,^ who showed that chloro- form, ether, and chloral hydrate diminish the oxidizing capacity of tissues. The theory of Baglioni indicates a possible mode of the action of narcotics after they have entered the cell. The other theories mainly pertain to the conditions which determine entrance into the cell substance. Reicher's Theory.^ — Beicher carried out a series of experimental studies on anesthetized dogs, in which he invariably found a considera- ble increase of the fat, or the lipoids, in the circulating blood. From this he drew the conclusion that the narcotic effect is not due to the fixation of the anesthetic in the lipoids of the brain, but rather to the ivashing out of the lipoids from the brain. The Meyer-Overton theory should accordingly be revised. Through the lipemia there occurs a profound impairment of the fat metabolism, which, in its turn, leads to acetone intoxication.^ Again, the acetone intoxication explains a part of the fundamental disturbances of the nervous system produced by the general anesthesia. The modification of the Meyer-Overton theory, as proposed by Eeicher on the basis of his findings, is as follows: The decisive factor for the efficiency of an anesthetic consists in its relative solubility in the lipoids. There takes place not simply a change of the normal physical condition, not merely a fixation in a sort of rigid solution, without the extrusion of lipoids from the cell; there occurs also an expulsion of vital lipoids and fats, in an as yet unknown mutual action between the anesthetic agent and the cell lipoids, this inter- action perhaps playing a part in the occurrence of the general anes- thesia; the lipoid remains for a long time chemically and microscopically demonstrable in the blood, as well as histologically demonstrable in the organs. Kramer's * experiments do not bear out Reicher's assmnption as to the cause of the lipemia. The explanation of this phenomenon, ^ Herter and Eichards: Am, J. Physiol., 12, 207. See also Wright: J. Physiol, 26, 362. ^ Eeicher, K. : " Chemisch-experimentelle Studien zur Kenntniss der ISTark- ose," Zeitschr. Min. Med., 1908, 65, 235. ^ These results refer to aliphatic derivatives. * ' ' The Eole of the Lipoids and Particularly Lecithin iu Narcosis, ' ' J. Exper. Med., 1913, 17, No. 2. 48 • ANESTHESIA according to Kramer, is still an open question, for from his observations he concluded: "1. The intravenous injection of five to thirty cubic centimeters of a 5 or 10 per cent emulsion of lecithin, depending upon the size of the animal used, does not interfere with the induction of anesthesia, and this can be accomplished as readily in animals thus injected as in controls. "2. In six out of nine experiments lecithin had no effect upon the rapidity with which the various phenomena which indicate the animal's recovery from the efEects of the anesthetic appeared."' Gros's Conclusions.^ — -Gros's experimental investigations of the rela- tionship of general and local anesthetics, on the basis of physical chem- istry, show that the latter have, in many respects, the same properties and effects as the former. General anesthetics possess the following three properties : ^ (1) A general action on protoplasm. (2) An elective action upon the nervous system, especially the central nervous system. (3) The possibility of restitution of the functions which have been disturbed by the anesthetic agent. Biirker's Theory.^ — According to Biirker, anesthesia is produced in such a way that, in the first place, the anesthetic agent accumulates especially in the nervous system, on account of its marked lipoid solu- bility. This accumulation, as such, does not suffice, but a chemical reaction results, the anesthetic agent appropriating the active oxygen. In consequence, this substance is withdrawn from the nervous tissue which is so arid of oxygen, and this oxygen deprivation leads to tem- porary asphyxiation, with paralysis of the physiological function. The products which originate in the oxidation of the anesthetic agent may be considered as partially responsible for the untoward after-effects of general anesthesia. This theory is based upon the following observation, as well as upon ' Gros, O. : "Ueber Narkotika und Lokalanesthetika, " Arch. exp. Path. u. Pharm., 1910, 63, 80. ^ These three properties are likewise found in the local anesthetics, cocain, encain, stovain, alypin and novocain, which are protoplasmic poisons. The more strongly a general anesthetic acts upon the central nervous system, the stronger is its action also as a local anesthetic. The theory of Meyer and Overton is also applicable to local anesthetics. As compared to general anesthetics, the local agents show the important difference that the sensory nervous system is more sensitive toward them, in a general way, than the motor nervous system. The anesthetic potential of the local anesthetic palt depends on that of the base and the degree of hydrolytic dissociation. ^Biirker: "Eine neue Theorie der Narkose, " Centralbl. Physiol., 1911, S4, 103; Munch, med. Woch., 1910, 27, 1445. GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 49 certain other well-known facts: When an electric current is passed through acidulated water, saturated with ether or some other anesthetic agent, only a very small amount of oxygen is liberated at the anode, the remaining oxygen being utilized for the oxidation of the ether, with the production of carbon monoxid, carbonic acid, acetaldehyd, etc. Biirker's experiments, in his opinion, are promising in regard to the rational selection of the anesthetic agents by means of electrolysis; and, at the same time, they elucidate the character of the oxidation processes in the living substance. It is also noteworthy, in this connection, that a — solution of grape-sugar (1.8 per cent) has practically no influ- ence upon the course of the electrolysis, in acid and neutral solutions, showing that the active oxygen alone is evidently insufficient for its com- plete combustion. The chemical indifference of the anesthetic agents, or a purely mechanical change in the condition of the plasma colloids, in the sense of Meyer and Overton, can hardly be admitted, according to Biirker, whose experiments indicate a temporary asphyxiation of the nervous system, in general anesthesia in the sense of Verworn and his school. The mechanism of this asphyxiation is suggested by the results of the -electrolytic experiments. The bad after-effects of general anesthesia are accounted for by the changed metabolism in general, which would be entirely inexplicable in the case of a chemical indifference of the anes- thetic agent. The metabolism is altered in a similar way as in diabetes, a disturbance of the normal oxidation processes being probably respon- sible. Verworn's Theory.^ — Verworn, in his recent monograph, contributes the result of his investigations, after ten years' work on the elucidation of the mechanism of anesthetics by means of experiments. On the basis of his findings, he groups anesthesia under the headings of the manifold paralyses which originate through a disturbance of the oxygen metahol- ism. General anesthesia is equivalent to asphyxiation of the tissues. This asphyctic state does not occur in consequence of the deficiency in oxygen as such, but it arises through the inhibition of the oxidation processes by the anesthetic agents. Accordingly, asphyxiation may also occur in the presence of abundant oxygen contents of the medium in the surroundings of the tissue or of the tissues themselves. In asphyxiation through the anesthetic the paralysis is acute; in asphyxiation in a medium free from oxygen the paralysis is more gradual in onset. In discussing the potential fashions in which the anesthetic, by pene- trating into the cell, suppresses its capacity for the production of oxida- tions, Verworn inclines to the explanation that the anesthetic agent pre- vents the transmission of oxygen from the medium and the reserve stores ^Verworn, M. : "Narkose" (Monograph), Jena, 1912. 50 • ANESTHESIA in the cell to the oxidizing materials. This explanation is most readily compatible with the laws of lipoid solubility and anesthetic action, for- mulated by Meyer and Overton; in this connection, Verworn assumes that the lipoids are in some way closely related to the oxygen carriers. In conclusion, the author explains the difference between sleep and general anesthesia : In sleep, a reaction takes place, with the assistance of the oxygen ; whereas, in general anesthesia, the restitution is inhibited through the prevention of the oxygen of the oxidation processes. Hence, these processes are radically different. Commenting on the view of Verworn, Lillie ^ points out that "cell- division — e. g., in developing egg-cells^usually ceases if the oxygen sup- ply is insufficient. Contractile activities are decreased or abolished. Many organisms, however, show only slight immediate effects; this is true of many Protozoa; Vorticellse, for instance, remain contractile for some time after simple removal of oxygen from the medium, although they are at once paralyzed by anesthetics. "Such facts oppose the view held by Verworn and others, that the anesthetic acts primarily on the oxidative mechanism of the cell. It is true that the rate of oxidation in active tissues is lowered during anesthesia, but this effect is rather a consequence than a cause of the lessened activity. Obviously wherever free oxygen is necessary to the normal activities of a tissue its withdrawal will arrest those activities. But the effects produced by lack of oxygen are not to be identified with anesthesia because of such incidental resem- blances." The Conclusions of Lillie."— Lillie has indicated that under certain well-defined artificial conditions, as well as under some that are normal, "the living system — organism, tissue or cell — becomes temporarily in- active and irresponsive to stimuli. When such an artificially induced state of inhibition is well marked and lasting it is called anesthesia, or, in a somewhat more restricted sense, narcosis. This condition may last for hours or even days, but apparently not indefinitely; and, when it passes off, the normal vital activities and properties return unimpaired. This apparently complete reversibility is one of the most remarkable features of anesthesia, and distinguishes it from death — a perhaps re- lated but characteristically irreversible change. The terms 'anesthesia' and 'narcosis' are somewhat differently applied, although they have the same essential significance; the former relates to any temporarily insensitive condition, however produced, while 'narcosis' usually means an anesthesia produced by chemical substances." Lillie used the term anesthesia to designate "any temporary or rever- sible lowering or loss of the normal vital responsiveness, or of the normal automatic vital activity, under the influence of certain artificial suh- ^ Science, n. s., 37, 959. 'Ibid., Nos. 965, 959-972. GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 51 stances or conditions. Anesthesia, as thus defined, may be exhibited by the most various organisms and cells, if not by all. It is fully as charac- teristic of plant cells as of animal cells, although its manifestations may be less obvious and striking in the former group of organisms. In its most familiar aspect the complete organism, e. g., a man, or an isolated living tissue, as a nerve or muscle, fails during anesthesia to show any response to a stimulus which normally excites it strongly. In other words, the capability of responding to stimuli — what we call 'irritabil- ity' — is in anesthesia diminished or lost. When the condition passes off the normal responsiveness returns unimpaired." ^ However, such decrease of the vital activity or responsiveness is not a solely artificial phenomenon. Conditions physiologically resembling anesthesia occur normally in the life of many organisms; sleep is, for example, a variety of physiological, regularly recurring narcosis, and all irritable tissues lose their responsiveness for a brief period following excitation. The last-mentioned state, the so-called "refractory period," has been compared with narcosis by some physiologists. There are also noteworthy resemblances between narcosis and fatigue. Thus the degree of irritability of a tissue may vary within a wide range under normal as well as artificial conditions. Lillie calls attention to a number of physical conditions which may deprive a cell temporarily of irritability; for example, mechanical shock and electrical currents may have this effect.^ ^ ' ' Thus a muscle exposed to ether vapor soon ceases to contract on stimula- tion; under the same conditions a nerv^e ceases to conduct; in motile plants like sensitive plants the characteristic osmo tic j noloi-mechanisms cease to act. Auto- matic activities like ameboid movement, ciliary movement, protoplasmic flowing, cell division, and growth may also be brought temporarily to a rest by anes- thetics. Claude Bernard showed that seedlings ceased growth in an ether-im- pregnated atmosphere, and resumed it when the ether was removed. Fertilized egg-cells cease to divide in the presence of an anesthetic in appropriate concen- tration, although they remain living and proceed with cell-division and develop- ment when the anesthetic is removed. Other less evident cell-processes, includ- ing metabolism, are similarly affected; the rate of oxidation is usually dimin- ished during anesthesia though there are exceptions to this rule. ' ' ' ' ' Under certain conditions the elect^-ie current may produce effects closely resembling typical anesthesia. (See Chapter XVI, p. 628.) This occurs when a weak constant current is passed through an irritable tissue like muscle or nerve; during the flow of the current the irritability of the tissue is modified in the neighborhood of the two electrodes, being heightened at the cathode and lowered at the anode; and in this latter region the nerve may become com- pletely insensitive to stimuli that ordinarily cause strong excitation. The inex- citable state thus produced is called " anelectrotonus " ; it is in reality a form of local anesthesia, and as such has been employed for the alleviation of pain in sciatica and similar conditions. Muscle is affected in a similar manner; the frog's heart may thus be rendered locally incapable of contraction, as in the simple class experiment familiar to all physiologists. This action of the cur- rent probably depends on its altering the electrical polarization normal to the 52 ANESTHESIA "Irritability may, however, be more readily modified by the use of chemical substances than by any other means, and, as is well known, many such substances are in daily use in medical and surgical practice for procuring local or general insensibility to pain — hence the applica- tion of the name 'anesthetic' to the large class of substances possessing this property." Before considering the mechanism of stimulation and of its modifi- cation by anesthetics, Lillie reviewed the most recent conceptions of the nature of the physico-chemical constitution of the living cell. He re- gards it as clear that the living protoplasm is a "polyphasic system," that is, a mixture consisting of various substances and solutions which are only partly miscible with one another, and are thus interrelated like the different phases of an emulsion or similar system. "These several phases, which are partly solid, partly liquid, appear in each living cell to have a constant and definite arrangement, whose exact nature varies characteristically from cell to cell. There appears typically to be a solid or semi-solid structural substratum consisting of colloidal material, most of which is in a water-swollen or hydrated state; in addition to this more fixed and permanent part of the cell organization, numerous sim- pler substances are present — sugars, salts, amino-acids and others — largely in a state of simple aqueous solution, but probably partly ab- sorbed at the surfaces of the colloidal phases. There is evidence that it is by the oxidation of certain of these substances, especially sugar, rather than of the colloidal material, that most of the energy manifested in the cell-processes is set free. The colloidal substratum furnishes the condi- tions under which the energy-yielding oxidations and other metabolic changes take place, and apparently determines their course, character, and velocity. The solid colloidal material of the cell may in one sense be considered as a by-product of the metabolic activities of the protoplasm ; it appears, once formed, to undergo itself relatively slight change, but to influence profoundly, by its presence and arrangement, the character of cell- metabolism. The colloids are of varied chemical nature; they are chiefly proteins and lipoids, and it is to be noted that they are built up by various forms of molecular union and polymerization from relatively simple substances furnished by the environment. This is true not only of plants, but also of the individual cells of higher animals, where the material which goes to form proteins reaches the cell in the form of amino-acids, or of simple polypeptides." membranes of the irritable elements — only in a direction the inverse of that causing stimulation. There is much evidence that the state of polarization of the semipermeable membranes bounding the irritable elements is an important factor in determining the degree of responsiveness to stimulation; the facts of electrotonus indicate that by altering the polarization by an external current the irritability of the tissue may be changed in the direction either of increase or of decrease." GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 53 "However simply organized a cell may seem, there are certain ele- ments of structure which appear always to be present, and to play a fundamentally important role in stimulation and in other life-processes. These are the membranes. Most, if not all, living cells are delimited from the medium in which they live by thin, semi-permeable colloidal surface-films, the so-called plasma-membranes. Similar semi-permealjle partitions are often found in the cell-interior, e. g., about nuclei, vacuoles, chromatophores, and other structures. They appear to be •formed of the same colloids as the other protoplasmic structures, namely, proteins and lipoids. These colloids, like many other organic substancesj" have, when dissolved in water, a marked influence in lowering the sur- face-tension of the solvent. Any substance thus acting tends, by the operation of Gibbs' principle, to collect or condense on the free surfaces ; if the substance is colloidal in nature it may there pass out of solution and form a solid surface-film or membrane; and it is probably under conditions essentially like these that the cell-membranes are formed. Artificial membranes similar in many of their properties to the plasma or nuclear membranes of cells may be formed in protein solutions about droplets of chloroform, mercury or other water-immiscible substances. Now the plasma-membranes of irritable cells undoubtedly play a funda- mentally important part in stimulation, as will be seen below, so that it will be necessary to consider first some of the essential properties of these membranes before passing to the consideration of the stimulation-process itself and its modification by anesthetics. "The plasma-membranes are typically semi-permeable structures — so much so that living cells form in many cases the most convenient and rapidly acting osmometers that we possess. Two provisos are necessary in making use of living cells as osmometers: first, the dissolved sub- stance must not by its own action impair the semi-permeability of the membrane, and, second, it must not appreciably penetrate the membrane during the time occupied by the experiment. The plasma-membranes are, in fact, semi-permeable only in relation to certain classes of sub- stances; toward others they show themselves freely permeable, and the character of these substances is important, because indication is thus afforded of the chemical nature of the materials composing the mem- branes.-'^ This, in Lillie's opinion, is a matter of fundamental impor- tance in the theory of anesthesia. "The plasma-membrane is characteristically and intimately con- cerned in the stimulation process. During stimulation it appears to undergo a sudden and quickly reversible increase of permeability. The electrical variation is one expression of this change, but there are others as well. Thus the movements of sensitive plants, which occur under the same conditions of stimulation as those of irritable animal tissues, are due to a collapse of turgid cells, consequent upon a sudden loss of the 54 ANESTHESIA semi-peraieable properties of the plasma-membranes enclosing the osmot- ically active solution or cell-sap. Here at least is one irritable tissue where the connection between permeability increase and stimulation seems unmistakable." With regard to why anesthetics interfere with the stimulation- process, Lillie pointed out that in the first place they can be shown experimentally to interfere with both of the characteristic manifestations of stimulation, (1) the action-current and (2) the change of permeabil- ity. If these are the critical or primary events on which the other effects following stimulation depend, it is evident that suppression of these must involve a suppression of the entire series of processes result- ing from stimulation, including the oxidations, the contraction-changes and the other special features of the response. That the action-current as well as the mechanical response of a muscle is suppressed by anesthetization has long been knoivn. In nerves also, anesthesia abolishes the action-current. On the foregoing hypothe- sis, the electrical variation is the expression of some alteration in the plasma-membrane, involving a temporary increase of permeability. Hober ^ has found that potassium salts, which deprive nerves of irritabil- ity and render them locally negative, cause at the same time a visible alteration in the axis-cylinders; these structures swell and stain more diffusely; he found further that these effects are checked or prevented if the nerves are first anesthetized with ethyl urethan. Experiments on voluntary muscle gave analogous results. If a frog's muscle is partly dipped into an isotonic solution of a potassium or rubidium salt the tissue contracts somewhat and becomes locally negative; this effect is also inhibited or retarded in the presence of an anesthetic. If the local negativity is the expression of a change produced by the salt in the col- loids of the plasma-membrane, rendering the latter more permeable than before, Hober's results indicate that the anesthetic decreases the sus- ceptibility to such changes of permeability. If this is the case we can partly understand why the anesthetized tissue becomes less sus- ceptible to stimulation, since stimulation involves an increase of per- meability. Lillie concluded that, if an anesthetic acts by so modifying the plasma-membrane of the irritable cell as to render difficult or impossible the rapid variations of permeability which are essential to stimulation," "it ought to act similarly on other cells, i. e., it should protect these cells also against the action of permeability-increasing substances or agencies. If an organism can be found whose cells undergo immediate and obvious increase of permeability under conditions which at the same time cause stimulation, it should become possible to determine whether suppressing the stimulating action of a given agency is equivalent to a suppression ^ See page 46. GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 55 of its permeability-increasing action. The two effects ought to sliow a definite parallelism if the above hypothesis is well based." Lillie investigated the antagonism between salts and anesthetics/ and his results may be summarized as follows : 1. In the action of pure isotonic sodium chlorid solutions on Areni- cola larvae the most evident effects are: (1) strong stimulation of the musculature, causing intense and prolonged contraction; (2) increase in the permeability of the pigment-cell membranes sufficient to allow visible exit of pigment; (3) immediate arrest of ciliary movement, fol- lowed by disintegration of the cilia; and (4) a general toxic action. 2. In the presence of a large number of anesthetics, in concentra- tions corresponding to those producing typical neuromuscular anes- thesia in sea water, all of these characteristic immediate effects of the pure salt solution are diminished or prevented. 3. In general, the permeability-increasing action and the stimulat- ing action of the salt solution undergo closely parallel decrease or pre- vention in the presence of the anesthetic. Prevention of sudden per- meability increase thus seems equivalent to prevention of stimulation; it is also equivalent to prevention of the immediate toxic action of the solution. The anti-stimulating and the anti-cytolytic effects of the anes- thetic thus show a definite parallelism. 4. In anesthesia the essential effect is a temporary alteration in the condition of the swface films or plasma membranes of the irritable ele- ments, of such a hind that these membranes no longer undergo, under the usual conditions of stimulation, the rapid increase of permeability essential to this process. 5. The membranes thus become during anesthesia increasingly re- sistant to permeability-increasing agencies: this involves increased resis- tance to those forms of toxic action which depend on destruction of the normal semi-permeability of the membranes. Hence the association of an anti-cytolytic or antitoxic action with the anti-stimulating action of the anesthetic. The observations made by Lillie also indicate that the degree of resistance of the membranes, and of other colloidal structures like cilia, is intimately dependent on the state of, their component lipoids. /,/ . Conclusions. — It appears to be established beyond doubt that the anesthetic is in solution in the blood during narcosis,^ and the thorough "^Am. J. Physiol, 1913, 31, No. 5, 255. See also Science, n. s. 57, Nos. 959, 764. , : -The investigations of Tissot (Compt. rend., 142, 234) show that in animal , rapidly anesthetized by chloroform the amount present in the blood may exceed 50 mg., more than 70 mg. per iOO c.c, and may even reach 70 to 80 mg. If, however, the anesthesia is slowly induced, it sinks to 45 or even 35 mg. More than 70 mg. per 100 c.c. ,of ;arterial blood often causes death. Tissot found that the amount in venous blood is always less than in arterial blood. His 56 ANESTHESIA investigations of Moore and Eoaf strongly point to the fact that an unstable compound is formed with hemoglobin, just as occurs in the case of proteid. It is probable that, in every case, anesthesia occurs when the unstable compound parts with the anesthetic to the cell proteids, and that penetration of the cells by virtue of the anesthetic to the cell lipoid occurs simultaneously. In this way, the relative power of the various anesthetics may be explained, for narcotic action is here dependent upon solubility in blood, stability of the compound, if any, formed with hemo- globin, rapidity of penetration of the cells, and nature of the solution in the cell lipoids. EFFECTS OF INHALATION ANESTHETICS UPON VARIOUS PARTS OF THE ORGANISM When a volatile agent such as chloroform, ether, ethyl chlorid or nitrous oxid is inhaled, the first action, naturally, is upon the respira- tory system. Passing from the air vesicles of the lungs into the pul- monary blood stream, the general anesthetic now acts upon the nervous mechanism, and, through this, upon the muscular and glandular struc- tures, the entire organism thus becoming more or less profoundly influ- enced. It is readily conceivable that the effects upon these interdepen- dent vital functions cannot be considered as isolated phenomena, but must be dealt with as correlated features of the complete mechanism of anesthesia. It is easily understood that it is impossible to trace the effects of the agent in successive steps and in a manner that is applicable to all cases. The phenomena may vary more or less with the agent employed, with the subject anesthetized, with the method of administration, and with various conditions. For these reasons, the discussion of the physiological action of general anesthesia upon the human subject must of necessity be general. The more specific action of the individual agents is given further consideration under the respective subjects. It is to be under- stood, furthermore, that the phenomena observed are those of a clinical character, rather than those noted by the experimental physiologist. Effects upon the Respiratory System. — The effect of anesthetic agents upon the respiratory system may be considered under two heads: (1) The primary or local action of the agent upon the upper respira- tory passages. (2) The secondary or general action upon the respiratory system, resulting from the stimulation of the respiratory center, and from the effect upon the muscular system, produced by the circulating anesthetic. Local Effect. — The direct action of the inhaled anesthetic upon the work seems to explain satisfactorily the cause of chloroform poisoning, espe- cially when considered in conjunction with the work of Moore and Eoaf. GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 57 respiratory passages may cause coughing, a sense of suffocation, and temporary suspension of respiration ("holding the breath"). General Effect. — This varies with the agent employed, the method used, the subject anesthetized, and other factors; it also varies with the stage of anesthesia. Ordinarily, particularly where the local effects are inconsequent, nor- mal respiration becomes deeper as the respiratory center is more and more profoundly influenced by the circulating anesthetic, and more rapid if an asphyxial element enters. During the earlier stages of anesthesia breathing may be interfered with by psychic impulses. This is particularly apt to be the case with nervous, excitable subjects, and those who, through fear, resist the action of the anesthetic. With nitrous oxid or other agents so administered as to cause a pronounced exclusion of oxygen from the respiratory apparatus, there is apt to be exaggerated or stertorous breathing, and the muscles of respiration are prone to assume a condition of tonic or clonic spasm. ( See Effects upon the Muscular System.) There may be temporary suspension of respira- tion (apnea), due, according to recent researches,^ to a fall of carbon dioxid pressure in the respiratory center, while the oxygen pressure is still sufficiently high not to give rise to excitement of the respiratory center. This condition, sometimes called "physiological apnea," may merge into true asphyxia in the event of "pushing" the anesthetic or of allowing undue physical constriction in any part of the respiratory tract. It is to be borne in mind by the anesthetist that the rate, rhythm, and amplitude of respiration are subject to various modifications by traumatic, thermal, and electrical stimuli. The interpretation by the administrator of the various respiratory sounds is discussed under administration. Effects upon the Circulatory System. — The effects of the anesthetic agent upon the Mood itself, upon the heart, and upon Mood pressure vary with the drug employed. The circulatory changes which are more or less characteristic in the different anesthetics will be considered more in detail under the special physiology of each agent. Experimental physiologists are not agreed concerning the various factors which influence the circulatory mechanism during inhalation anesthesia, nor are they agreed with reference to the effects of the anes- thetic agent upon the blood itself. Certain data are sufficiently well established, however, to be of practical value, and to these attention will be confined. The only changes produced in the chemical composition of the blood by the circulating anesthetic, according to many physiologists, are those arising from a diminished supply of oxygen. It has been claimed, how- ever, by other investigators, that the hemoglobin content of the red ^J. Fhysiol, 32, 225. 58 ANESTHESIA corpuscles is markedly decreased; that there is destruction of the red corpuscles (DaCosta), and that the urobilinuria which may occur two or three days after anesthesia is probably the result of this destruction. It is also claimed that lecithin and cholesterin are increased, fat, according to Eeicher, being increased up to two or three times the normal amount. Disintegration of the fat and albuminoid bodies is sufficient to lead to the increased secretion of acetone. The specific gravity of the blood commences to rise shortly after the beginning of the operation, the in- crease continuing for several days thereafter, according to observations made by Sherrington and Copeman ^ on healthy animals. Poggiolini ^ investigated the morphological changes of the blood, in ether and chloroform narcosis, in a series of experiments on healthy rabbits. The different results which have so far been obtained in the examination of the influence of ether or chloroform narcosis upon the blood are referred by him to the fact that the influence of existing dis- eases, of the operation itself, and of the binding of the animal have not been sufficiently considered. His experimental findings led him to the following conclusions : The changes of the blood constituents, noted after ether or chloro- form narcosis, are independent of the duration of the narcosis, of the quantity of the narcotic, of the frequency of the narcosis, and of the time-interval between the individual narcoses. Deep narcosis, with ether or chloroform, induces leukocytosis, of variable duration and degree. At the same time, the relative composition of the leukocytes is changed, either the lymphocytes or the neutrophile polynuclear cells undergoing an increase. The change of the leukocyte picture persists for a longer time in chloroform narcosis than after ether narcosis. The red blood corpuscles and the hemoglobin present rather variable changes, inde- pendent of each other, after the two narcoses. However, after chloro- form narcosis there are regular destructive and retrogressive changes of the red blood corpuscles, which are absent after ether narcosis. Accord- ingly, inhaled chloroform appears to be more toxic, and of a more pro- longed action, than ether, in the opinion of Poggiolini. The psychic state influences the circulation in the initial stage of anesthesia, as manifested by pallor, lividity, syncope, and even death. The cardiac and vasomotor centers are more or less frequently influenced in such cases, these exigencies being more apt to occur in nervous and excitable patients, particularly those who are frightened before begin- ning the inhalation. Just as the efficient function of the respiratory system during anes- ^ Sherrington and Copeman : ' ' Variations Experimentally Produced in the Specific Gravity of the Blood," J. Physiol., 1893, 14, 52. See section on "Shock." 2 Poggiolini : " Le modificationi morphologiche del sangue nella narcosi eterea e nella cloro-narcosi, " II Policlinico, 1911, Sez. Chir. 18, 3-5. GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 59 thesia is dependent, in part, upon the circulatory system, so is the proper condition of the circulation dependent upon respiration. Obstruction of the respiratory passages, however slight, has its concomitant circulatory disturbance. A slight degree of obstruction gives rise to a corresponding degree of venous congestion, manifested by freer bleeding at the site of operation, and perhaps by the swelling of the tongue and adjacent parts, these changes being greater in some subjects than in others. The action of the anesthetic upon the heart may be primary, but, as a rule, it is secondary. The muscles of the heart, as well as those of the arterioles, are directly affected by the anesthetic, the effect varying according to the particular agent, the method of administration, and the extent to which it is carried. The effect may be that of direct stimula- tion (as with ether) or of direct sedation (as with chloroform). Changes in the blood pressure are dependent upon the anesthetic employed and the body position. With nitrous oxid there is a marked rise in blood pressure; with ethyl chlorid there is, according to some observers, a slight rise, according to others none; with ether there is first a rise and then, with deep narcosis, a slight fall; with chloroform there is, according to universal agreement, a fall in blood pressure. The mechanism of the rise or fall is a disputed point. Some physiologists have maintained that the fall is the result of direct vascular dilatation; others hold that it is due to dilatation of nervous origin. Kecent experi- ments tend to establish the correctness of the former view. Various other factors influence the circulation during anesthesia, such as hemorrhage resulting from the operative procedure, the position of the patient, deep breathing, and positive pressure. According to Eppinger and Hofbauer,^ "the pulse in patients whose diaphragm was unusually high or low showed that the circulation in the legs was better when the diaphragm was high, as the quadrate foramen was thus left open. When the diaphragm is low, this foramen is more squeezed together and the flow of blood up from the lower part of the body is thus impeded. At the same time, deep breathing pushes the diaphragm low down and it thus presses on the liver and liver veins and thus promotes the circulation in the region." Effects upon the Muscular System. — The effects of inhalation anes- thetics upon the muscular system may be considered under two head- ings: (1) Direct, which are of interest to the experimental physiologist rather than to the practical anesthetist, inasmuch as they involve the direct contact of the muscle with the anesthetic agent, a contingency which does not normally arise in clinical work. (2) Indirect, which are of nervous origin. The indirect muscular phenomena of general anesthesia are almost ^ ' ' Kreislauf und Zwerchfell, ' ' Zeitsch. f. Min. Med., 72, No. 1. 60 ANESTHESIA entirely controllable by certain methods of administration, to which reference will be made in detail later. Under these circumstances, namely, the administration of oil of bitter orange peel as a preliminary to the anesthetic agent, the conscious voluntary movements of the pre- liminary stages of narcosis are practically held in abeyance. The un- controllable muscular movements in the stage of excitement are absent because there is no such stage. Subconscious purposive movements and simple tonic spasm, local or general, are not noted. The coordinated movements sometimes noted in deep anesthesia as ordinarily induced are absent, as are likewise the tremors of moderate narcosis. The usual conscious, subconscious, and unconscious movements, the tremors and clonic spasms noted during the administration of any of the inhalation anesthetic agents, or the ordinary combination of these, are more or less completely held in abeyance by the action of oil of orange, administered as a preliminary to these agents. (See Preceding the Ad- ministration with Oil of Bitter-Orange Peel, p. 91.) For further details concerning effects upon muscular system, see Special Physiology of each agent. Effects upon the Glandular System. — The effects of general anes- thetics upon the glandular system may be considered under two heads: (1) The immediate effects, or those noted during the administra- tion, (2) The secondary, or after-effects, or those observed after the sub- sidence of anesthesia, when the anesthetic agent is no longer circulating in the blood. Both the immediate and the after-effects vary with the anesthetic agent, with the method of administration, with the degree to which nar- cosis is carried, and with various other factors to be discussed more in detail under the special physiology of each anesthetic. The immediate effects involve particularly the mucous, salivary, sweat, and lachrymal glands. The secretion of mucus and saliva is greater during light and moderate narcosis, whereas it is decreased dur- ing the deeper stages. The same holds true with lachrymation with all the general anesthetic agents. The sweat glands are more or less affected in the various stages of narcosis by the different anesthetics. In the presence of cyanosis or severe shock with any agent, the sweat glands become hyperactive, as evidenced by the ''cold perspiration" which sub- sides with the restoration of proper respiration and circulation. Eenal function is interfered with during the administration, accord- ing to some observers, being increased up to the point at which the corneal reflex disappears and completely arrested during profound anes- thesia. This decreased secretion of urine during the administration may continue to the point of complete suppression, resulting in death. Vari- ous intermediate degrees of suppression and concentration, with in- GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 61 creased chlorids, phosphates, urea, casts, and albumin in greater or less quantity, have been noted, the urine gradually returning to normal within a week after the anesthesia. These observations apply to chloroform and ether. Tlie occurrence of albuminuria during the administration of inhalation anesthetics is said to occur with some of the agents and not with others. Fatty degeneration of the liver, kidneys, heart, and other organs may occur, particularly after repeated administrations of chloroform, unless safeguarded by heat, moisture, oxygen, and rebreathing, together with enemas of normal saline, olive oil, and glucose.^ Effects upon the Nervous System. — The sequence in which the parts of the nervous system are involved in the production of general anesthe- sia is still the subject of discussion among experimental physiologists as well as practical anesthetists. English and American investigators hold that the cerebral cortex is first involved; the basic ganglia and cere- bellum,^ second; the sensory centers of the cord which connect the brain with the periphery, third; the cerebro-spinal motor tracts and centers, fourth; and the respiratory, vasomotor, and cardiac centers of the medulla, fifth. Inhibition of all functions, and death, folloAv. Accord- ing to Dastre and other French observers, the sensory nuclei of the cord or the cerebral ganglia are affected before the cortical centers are involved. The order in which the special senses are affected by the general anes- thetic cannot be definitely stated. The majority of observers seem to be agreed that sight is lost before hearing, and that taste persists longer than either of these. With nitrous oxid, hearing is the last sense to disappear and the first to reappear. The sense of smell is very easily lost, as is witnessed in the effect of oil of bitter orange peel, to which reference has been made. The refiex phenomena of general anesthesia may occur during any stage of narcosis, from the beginning of the induction period to the period immediately preceding inhibition of respiration. They vary con- siderably with different patients. The refiex circulatory phenomena are of special importance from a practical point of view. They may arise during all stages of anesthesia, and they may vary in intensity from slight reflex vasomotor stimulation ^ See Chapter on Treatment, Preliminary, During, and After Anesthesia. ^Francis and Fortescue-Brickdale ("The Chemical Basis of Pharmacology," 1908, 81) state that the physiological action of the entire group of aliphatic nar- cotics is first on the higher centers of the cerebrum, then on the lower centers of the medulla and cord. Eventually, continue these authors, the reflexes are completely abolished, and this constitutes an important distinction between this group and the alkaloidal narcotics, of which the principal representative is mor- phin. In large doses morphin increases reflex irritability, and in smaU doses does not depress it. 62 ANESTHESIA or inhibition, with consequent rise or fall of blood pressure during the earlier stages, to profound circulatory shock during the stage of deep narcosis. They vary with the anesthetic employed, being more com- monly manifested with chloroform than with ether ; with the method of administration, being largely eliminated by the modern methods (see Chapter VIII) ; with the degree to which the anesthesia is carried; and with the state of the nerve centers (vasomotor, cardio-inhibitory, cardio- accelerator) acted upon by the anesthetic agent. Eeflex circulatory disturbances of a serious nature, occurring during the earlier stages of anesthesia, before consciousness is entirely lost, are often of psychic origin. It is important, for this reason, that the sur- gical procedure be not commenced until anesthesia is complete. The occurrence of circulatory shock after the induction of general anesthesia has been the subject of much serious investigation, the work of Crile ^ being particularly noteworthy.^ Eeflex respiratory phenomena are more frequently present during the lighter than during deeper degrees of narcosis. It is to be borne in mind, however, that the psychic stimuli of the conscious stages of anes- thesia may give place to the traumatic stimuli of the stage of surgical anesthesia. These stimuli, applied in any part of the body, may cause reflex spasmodic movement of the tongue, whereby this organ is drawn over the laryngeal orifice, giving rise to laryngeal spasm, respiratory and expiratory spasm, coughing, retching, and stertorous breathing. When these phenomena assume a serious and menacing character, the condition is described as "respiratory shock." This is most apt to supervene during moderate anesthesia. FACTORS WHICH MAY BE SAID TO MODIFY THE PHYSIOLOGY OF ANESTHESIA AS ORDINARILY INDUCED It has been suggested ^ that the phenomena resulting from the ad- ministration of inhalation anesthetic agents more properly come under the head of pathology than of physiology. However this may be, certain it is, as elsewhere stated, that practically every phenomenon varies with the particular anesthetic agent administered, with the general condition of the patient, with the condition of the blood, and with various other factors. For these reasons, it has been deemed advisable to consider here cer- tain factors which, introduced into the administration of inhalation anesthetics, may be said to modify, to a more or less pronounced degree, ^ Grile, G. W. : " Surgical Shock. ' ' Also, Boston Med, and Surg. J., March, 1903. '' Chapter on Treatment, p. 41. 3 Wright, Hamilton : Loc. cit. GENERAL PHYSIOLOGY OF INHALATION ANKSTilKSlA 63 some of the phenomena ordinarily ohserved, and commonly considered under the head of physiology. These factors are : 1, Warming the agent; 2, utilizing moisture; 3, combining oxygen with the agent; 4, preceding the administration with oil of bitter orange peel; 5, utilizing carbon dioxid; 6, rebreathing.^ The consideration of these factors, particularly the first, necessarily involves the introduction of a certain amount of technique, which, of itself, would no doubt more properly come within the chapter on Ad- ministration, or perhaps Special Physiology. The following discussion may be considered, therefore, as an addendum to General Physiology. Warming the Agent. — The value of warmed anesthetics has been recognized by many anesthetists since Clover ^ devised his double- current apparatus, by means of which the expired air warmed the anes- thetic agent. Since that time various attempts have been made to deliver to the patient warmed ether or other agent,^ but in each instance the apparatus was found to be inadequate, too complicated for practical use, or otherwise unsatisfactory. It was not until 1905, however, that systematic laboratory experi- ments and clinical observations were begun,* with a view to determining the relative value of the various inhalation anesthetics when these are administered cold and when they are warmed to the temperature of the blood (98.6° P.). These observations were made by Gwathmey par- ticularly with reference to: (1) safety as regards life; (2) the main- tenance of body temperature, and the consequent lessening of the danger of shock; (3) recovery from the anesthetic; and (4) after-effects. Other phenomena were also noted. Safety to Life. — First, with chloroform: In order to determine the value of chloroform as regards life when heated to 100° F. and at room temperature, Gwathmey ° made a number of experiments, using compressed air and passing this air through chloroform at room tem- perature and then to a special animal mask, using a Junker inhaler for the chloroform. He found that it took 6.57 minutes on the average to kill sixteen animals. Employing the same technique with the addition of another Junker inhaler, filled with warm water and placed in a warm receptacle between the chloroform and animal mask, he found that the average time required to kill seventeen animals was 20.35 minutes,'^ thus ^ Chapter on Eebreathing. = Clover: Brit. Med. J., March 15, 1873, 282; July 15, 1876, 74; Jan. 20, 1877. '(1) Hawksley: Brit. Med. J., Aug. 2, 1873, 177. (2) Foy: "Anesthetics, Ancient and Modern," 141. * Gwathmey: Med. Bee, Oct. 14, 1905; N. Y. Med. J., Feb., 1908; J. Am. Med. Assn., Oct. 27, 1906; Am. J. Surg., July, 1908. See also Coburn: Med. Bee, March 1, 1913. '^ For technique, see p. 317. *See table, p. 64. 64 ANESTHESIA showing that chloroform at blood temperature is three times as safe as chloroform at room temperature. TIME EEQUIEED TO KILL ANIMALS WITH CHLOROFOEM AND AIE No. of minutes required No. of minutes required No. of experiment to kill at 100° F. to kill at normal ^ temperature 1 18 4.5 2 57 3 3 26.5 7.5 4 24.5 7 5 15 4 6 16 4 7 15 3.5 8 8 7.5 9 13 9 10 22 5.5 11 12 7 12 17 10 13 21 6 14 25 9 15 27 10 16 17 7.5 17 12 17)346 16)105 20.35 6.57 Second, with nitrous oxid and oxygen instead of chloroform, and passing the mixed gases through a tube, first at room temperature, and then surrounding the tube with hot water, and, last, surrounding the tube with ice, and in all instances measuring the temperature accurately by a thermometer placed in a bent tube, using the same animal mask and giving all animals first six per cent of oxygen with nitrous oxid for five minutes, and then reducing the amount of oxygen to three per cent, the following results were obtained: Twelve animals were anes- thetized and killed by nitrous oxid and oxygen at room temperature. The average time for the eye and extremity reflexes to be abolished was 4 minutes. The average time required to kill was 9 minutes and 20 seconds. The shortest time was 4 minutes and the longest 12 minutes. Nine of these animals struggled violently until anesthetized; two were quickly asphyxiated; one weakling remained quiet after two minutes. In all cases, heart action, rapid at the start, ran from 150 up to 200 during the frightened struggles; as anesthesia progressed, it again became irregular, with marked second sound accentuation, and very rapid and weak Just before death. The respiration in all cases was irregular, and gasping to variable degrees. In all cases tonic convul- sions occurred just before death. In 25 per cent of the cases convulsions occurred during the first three to five minutes (probably anoxemia ) ; GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 65 continuation of heart action after respiration ceased: average time, 2 minutes; longest, 3 minutes; shortest, 1 minute. Twelve animals were anesthetized with warm nitrous ox id and oxy- gen by having the tube containing the mixture of gases passed through a hot water bath kept at a temperature of 98° C. The same proportions were used as in the administration of the cold gases. In all other re- spects the technique was the same as far as the experimenter could possibly make it. Abolition of Eeflexes. — Two animals (weaklings), anesthetized with 6 per cent oxygen mixture, lost their reflexes at the end of 5 minutes; 6 animals had reflexes abolished with the 3 per cent oxygen mixture in 13 to 25 minutes, the average time being 18 minutes. Four were not anesthetized at the end of 30 minutes. After the removal of the inhaler, 2 were able to walk in from one to two minutes. The other 2 were killed. Eight animals were killed by the anesthetic ; the average time was 18 minutes. Four were in good condition at the end of 30 minutes; two were disposed of as noted above; and two were put away for future work. The shortest time was 12 minutes; the longest time, 28 minutes. Eight struggled from 1 to 3 minutes because held, and the remainder did not struggle after the first few breaths. Heart Action". — After preliminary excitement, action was regular in force and frequency until death approached, when it became rapid and weak. Eespieation. — In all cases respiration was quiet and regular after the first few minutes, becoming gasping just before death. Convulsions. — No early convulsions occurred. Mild tonic convul- sions occurred just before death. Continuation of heart action after cessation of respiration: average, 3^ minutes; shortest, 2 minutes; longest, 5 minutes. The third series of experiments was conducted in precisely the same manner as the first two, as regards technique, percentage of oxygen, etc., with this difference: the tube containing the mixture of gases passed through a vessel packed in ice. The U-shaped tube containing the ther- mometer was also packed in ice. The thermometer did not vary from 33° to 34° F. during the administration. Ten animals were killed. The results were as follows : After eight to ten breaths of this cold mix- ture, violent struggling ensued and breathing ceased almost immedi- ately. Fibrillary twitchings greatly resembling a chill occurred in all animals after the first minute of inhaling the mixture. The average time required to kill was 5 minutes and 31 seconds, or about 4 minutes less than at the normal temperature, and 13 minutes less than the S animals killed by the warmed gases. The shortest time was 3 minutes and 55 seconds; the longest time, 7 minutes. From the above, it will be seen that warmed nitrous oxid and oxy= 66 ANESTHESIA gen is much safer than using this mixture of gases at the room tempera- ture, and very much safer than the cold gases. The following case history illustrates very clearly the difference be- tween cold and warm nitrous oxid and oxygen as observed in the human subject. A large number of similar histories could be cited. Female. Age, about 45 years. April 19, 1907. Patient was given 1/4 grain of morphin and 1/150 grain of atropin thirty minutes before the operation. Operation (laparotomy) lasted two hours, during the whole of which time the patient was kept under the influence of nitrous oxid and oxygen, without the aid of any other anesthetic. A fibroid tumor weighing thirty-five pounds was removed. At the end of one hour the anesthetist's (J. T. G.) gas tanks became exhausted, and he was compelled to use the hospital tanks, which unfortunately were of such size and condition that he could not use his hot-water attachments. As soon as he began using the cold gases, the respirations showed a marked decrease in number and were slightly labored, but, with this exception, the narcosis was entirely satisfactory, the patient making an uneventful recovery and without nausea or vomiting. Third, with ether: Only a few experiments were conducted with ether, but the number was sufficient to fully convince one that warm ether acts similarly to warm chloroform and warm nitrous oxid; that is, it is twice as safe, as shown by the fact that it took over twice as long to kill the animals with warm ether vapor as with cold. Fourth, with ethyl chlorid: We have made no experiments with warm ethyl chlorid, but by analogy we may conclude that, as chloro- form, ether, and nitrous oxid are increased in value by heat, the value of ethyl chlorid would likewise increase. From the animal experiments with the different anesthetics, i. e., chloroform, ether, and nitrous oxid and oxygen, first at the room tem- perature, and then heated to the temperature of the blood, and finally with nitrous oxid and oxygen at -|- 33° to -|- 34° F., we conclude that all anesthetics heated to the temperature of the blood are increased in value as regards life, without decreasing their anesthetic effect. From these experiments it is also evident that to these highly sensitive creatures the warm gases were much pleasanter to inhale. From clinical experi- ence it can be stated positively that the facts learned in the laboratory are beyond all question true also in practice. The Maintenance of Body Tempeeature. — A large number of observations have been made with reference to the effect of narcosis upon the body temperature.^ The loss of body temperature observed in all ^Kapeler: " Ansesthetica, " Deut. Chir., 1880, 33, 168; Hare: "Experi- ments to Determine tlie Influence of Etherization on the Normal Bodily Tem- perature, etc.," Therap. Gaz., 1888, 1^, 317; Dastre: ''Les anesthetiques : physiologie et applications chirurgicales, " Paris, 1890; Allen: "Effect of GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 67 instances, both in the experiments upon animals and in clinical observa- tions upon the human subject, has been variously explained as being due to diminution of oxidation, to radiation of heat from uncovered portions of the body, to the effect of the anesthetic agent upon the regulatory centers, to the increased output of heat in consequence of dilatation of the cutaneous vessels, etc. Whatever the cause of this loss of body temperature, it is interesting to note that even a fraction of a degree of elevation of temperature of the anesthetic agent above that of the room will have a marked effect in maintaining the body temperature of the patient. The author's observa- tions in this regard have been amply verified by those of Davis,^ both upon animals and upon human subjects. 'In twenty-six patients anesthetized with warm ether vapor, there was a loss of body temperature averaging .29° F. as against the loss of 1.02° F. in one hundred and forty cases anesthetized under similar con- ditions with the open drop method. The shortest period of anesthesia in which the temperature was noted was forty minutes, the longest four and three-quarter hours. The temperature was taken by rectum imme- diately before starting and immediately after the removal of the anes- thetic. These experiments of Davis upon human beings undergoing surgical operations are most conclusive. The practical application of this lies in the fact that in the majority of instances the patient's temperature is necessarily lowered by the surgical operation, and also by the anesthetic as usually administered. In this connection it may be well to emphasize the fact, mentioned by Davis,^ that an undue elevation of the body temperature, as a conse- quence of employing a warmed anesthetic agent or as a result of other measures, may prove injurious. In one of his animal experiments the body temperature of the subject was elevated by means of an electro- thermal pad and blankets. There was a rise of 4.14° F. in one and three-quarter hours, at which point death suddenly occurred. An over- dose of ether was a presumptive factor, but the chief factor was thought to be this great increase in temperature. The following are the charts of two human subjects, in which death was supposed by Davis to have been caused by giving a warmed anes- thetic for too long a time. In the second case, that of a child five months old, it would seem that the shock from too long an anesthetic Anesthesia upon the Body Temperature and Blood Pressure," Trans. Am. Surg. Assn., 1896, 14, 367; Morley: "The Effect of Anesthesia upon the Body Tem- perature," Am. Gynecology, 1903, No. 3, 300. ^ Davis: "On the Effect of Narcosis upon the Body Temperature," Johns EopMns Eosp. Bull., April, 1909, 118. '^ Loc. cit. 68 ANESTHESIA and not the warmed ether vai3or was the immediate cause of death, following are the records : ^ The Name — H. G. Address — Johns Hopkins Hospital, Age — 35. Surgeon — Gushing. Operation — Gerebellar Exploration. Anesthetic — Ether Vapor Warmed. Amount — 225 gm. Temp, before anesth. — 38. Temp, after anesth. — 40.44. Temp, operating room — 31.1 CASE 1 Sex—M. Date— October 7, 1908. Method — Open. Duration — 3 hours. Narcotics — None. StimMants — None. Complications. Temperature two hours after the anesthetic, 41.3°. Patient died one hour later. CASE '2 Da^e— May 29, 1908. Weight — Name — C. C. Address — Johns Hopkins Hospital. Age—b M. Sex—M.. Surgeon — Gushing. Operation — Spina Bifida. Anesthetic — Ether Vapor Warmed. Method — Open. Amount — 50 gm. Duration — 2i hours. Temp, before anesth. — 38. Narcotics — None. Temp, after anesth. — 39.8 Stimulants — None. Temperature operation room — 29.5. Complications Anesthesia ended 5.00 p. m., Temperature, 39.8. 5.30 p. m., Temperature, 40.5. 6.00 p. m., Temperature, 40.1. 6.30 p. m., Temperature, 40.2. 7.00 p. m.. Temperature, 40.5. 7.30 p. m.. Temperature, 40.8. 8.00 p. m.. Temperature, 41.4. Died, 8.25 p. m. It may be interesting in this connection, before considering the ques- tion further, to note some observations concerning the temperature stim- ulus as applied to certain agents. ^Private communication from Dr. Davis. GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 69 Hoffmann/ in his discussion of the cooling-off of the inspired air and its causative connection with post-operative pulmonary affections, says that, in the ether-drop-anesthesia according to Witzel, there occurs an automatic regulation of the ether contents of the inspired air. This self-regulation is brought about through a considerable refrigeration of the temperature of the inspired air. This cooling can be avoided with- out disturbance of the automatic regulation, by the utilization of a suitable mask. Stursberg - discussed the behavior of blood pressure under the action of temperature-stimuli in ether and chloroform anesthesia, as well as its bearing upon the occurrence of subsequent complications. In ether nar- cosis it will be found that a cold stimulus is followed by vascular con- traction, possibly without a later reactive dilatation, thus supplying the conditions for "catching cold." The action of chloroform, Stursberg found, is not generally followed by extensive vascular contraction on the refrigeration of the skin; con- sequently, the distribution of the blood is not altered in the sense of an induced hyperemia of the internal organs, which does away with a condi- tion favoring the origin of "colds." Eecovery from the Anesthetic. — With the idea of testing the influence of heat upon the recovery of the subject from the anesthetic, Gwathmey anesthetized three animals at the same time, under glass receptacles, for ten minutes, afterward placing them in receptacles, one at 0° F., another at 100° F., the third being allowed, as a control, to come out in the room temperature. The animals were changed in posi- tion on three successive days. In each instance, the animal in the warm chamber made a slightly more rapid recovery than the others. The ani- mal in the cold box came out in chills, while the one in the room tem- perature came out a close second to the one in the warm box. With reference to human beings, it may be stated that, by applying hot towels to the patient's face, or by aerating the lungs with hot air toward the close of any anesthesia, the patient recovers quickly from the anesthetic. It will thus be seen that recovery from the anesthetic is facilitated by the natural inhalation of warmed atmospheric air, or by the artificial introduction into the lungs of a current of warmed air. Experimental and clinical observations have abundantly verified these findings with reference to the use of warmed anesthetics. ^ Hoffmann, M. : " Ueber die Abkiihlung der Inspirationsluf t bei der Aethertropf narkose, ihre Bedeutung und ihre Verhutung, ' ' Mittlg. a. d. Grensgeb. d. Med. u. CUr., 1910, 31, 869. - Stursberg, H. : " Ueber das Verhalten des Blutdruckes unter des Einwirkung von Temperaturreizen in Aether und Chloroform Narkose, ' ' Mittlg. a. d. Grens- geb. d. Med. u. CUr., 1911, ^f, 1. 70 ANESTHESIA After-Effects. — A great deal has been written, by many investi- gators, concerning the immediate and delayed after-effects associated with inhalation anesthesia. Observations made by Clover and others of the earliest workers in this field tended to prove that the after-effects are lessened when a warmed vapor is used. Subsequent laboratory experi- ments and clinical observations have amply verified these findings. A warmed vapor (provided it is not too warm) gives rise to less irri- tation to the air passages, and thus decreases, the danger of post-anes- thetic bronchitis and pneumonia. The warmed vapor, being less irritating to the buccal mucous mem- branes, causes less stimulation of the salivary and mucous glands, and consequently there is a less profuse secretion of saliva and mucus than is apt to occur when cold vapor is administered. The anesthesia, there- fore, is accompanied and followed by less nausea and vomiting than occur as a consequence of the hypersecretion of these nauseating fluids when a cold vapor is employed. This observation is particularly striking with ether. The late after-effects, such as acid intoxication and its consequences, have received voluminous attention from many observers, among whom there is no unanimity regarding the cause of these manifestations. Doubt has been expressed by some concerning the existence of such sequels. Idiosyncrasy, gastro-intestinal disturbances, preexisting met- abolic fault, nervous influence, and failure of complete elimination of the agent from the blood, with consequent degenerative changes in the vascular elements and other tissues, are some of the explanations offered. Whatever the cause, it seems to be fairly well agreed that acidosis, and other late after-effects, occur in a certain proportion of cases. With the administration of warmed anesthetics, according to the method described in the section on Administration (p. 63), both the immediate and the delayed after-effects are reduced to a minimum.^ Experiments on Warming Ether. — It is maintained by some investi- ^ It has been known for a long time that during chloroform and ether anes- thesia the temperature of the body is lowered, and the opinion has been ad- vanced that the great fall of temperature may be partially responsible for the development of pneumonia. A. Lawen {Miinch. med. Woch., 1911, 2097) has studied the question as to whether post-operative pneumonia can be avoided by warming the anesthetic prior to its inhalation. He therefore experimented with an apparatus by means of which the chloroform and ether vapors could be warmed. His results show that pneumonia cannot be thus avoided, though he does not doubt that a small proportion of cases of post-operative pneumonia may be prevented by the pro- posed modification of the method of inhalation anesthesia. He considers that the warmed anesthetics are only suitable for prolonged abdominal operations, and for operations in which the wounds are extensive, such as in amputation of the breast. He also considers the warmed anesthetic to be indicated for patients who have lost much blood or who are suffering from shock. GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 71 gators that ether vapor cannot l)e heated. iSeelig' eondueted a .series of experiments for the purpose of estahlishing the (;orrcctncss of this view. The authors of this hook, wishing to settle the disputed point with reference to the possibility of heating anesthetic vapors, undertook a series of experiments to determine whether the vapor is really warmed by being passed through a coil ten feet long placed in a heater, according to a method in actual practice. A rubber tube, of the same length as that used in actual practice, with a thermometer placed at one end and also a tliermometer for room Fig. 11. — Gwathmey's Vapor Apparatus with the Tube Leading from the Heater AS IN Actual Practice, a. Compressed air; b. Gwathmey anesthetic apparatus; bi. ether container; bh. water; b. ether vapor exit; c. vapor heating apparatus; ci. elec- tric hot plate; c". asbestos mat insulator; c"i. water bath; c'^. thermolite heater; c'. inlet to heater; d. exit for heated vapor; e. asbestos insulator; f. 60 cm. rubber tube; G. glass T-tube; h. 200° C. thermometer; i. drain; k. thermometer for room temperature. (From S. G. Davis.) temperature, was employed (see Fig. 11). Compressed air was passed through for one hour. (Joss - has found that ether cools the air inhaled 33° to 44° F. below the temperature of the room. The cooled air undoubtedly lowers the resisting powers of the cilia of the ciliated epithelium lining the upper air passages when these passages become chilled. Infection is more likely to find its way into the finer air passages as salivation increases under the chilled anesthetic.) These experiments gave the following data: From Table 1 it will be seen that the temperature of the ether vapor can be raised to any degree desired and maintained at that point. The vapor may be heated by difl^erent methods, but this is probably one of the easiest, as with this simple apparatus one is not dependent upon electricity as the heat source. ^Seelig, M. G.: "The Fallacy of Warmed Ether Vapor," Inter. Med. J., Sept., 1911; see also. Cotton and Boothby: "The Uselessness of Warming Anaesthetic Vapor," Surg., Gyn. and Obst., Dec, 1912. ^Mitteil. a. d. Grenzgeh. d. Med. u. Chir., 22, No. 40. 72 ANESTHESIA TABLE 1 — Using Rubber Tube with Continuous Flow Amount of ether taken, 4 ounces. Amount of ether used, 3.5 ounces in one hour. Compressed air flow, continuously through ether. Room temperature, 24° C, Nov. 4, 1911. After 5 minutes . . . 29.25° C. ] After 10 minutes . . . 29° After 15 minutes. . . 31° After 20 minutes . . . 31° Ether container Temperature, After 25 minutes . . . 30° warmed as is 65 cm. from heater - After 30 minutes . . . 30.25° necessary. (usual distance) After 35 minutes. . . 32.25° Heated ether After 40 minutes . . . 32° container. After 45 minutes . . . 32° After 50 minutes . . . 30° . After 55 minutes . . . 30° J In order to determine the temperature of ether at different distances from Davis' heater, which was attached to the Gwathmey three-bottle vapor inhaler, a series of experiments were conducted in the chemical Fig. 12. — Gwathmey's Vapor Inhaler with Heating Apparatus, f. Glass tube di- vided into six parts of 10 cm. each; f.' thermometers; i. drain; k. thermometer for room temperature; e. asbestos insulator. laboratories of the College of the City of New York by the authors. The experiments were carried out by Mr. W. A. Hamor. A special glass tube was constructed with uniform side tube openings 10 cm. apart, into which thermometers were inserted (see Fig. 12). At the side-tube exits and over the thermometers, a tightly fitting rubber collar was placed to prevent leakage. The glass tube was attached to a thermolite coil-heater, immersed in a water bath, which was kept at the GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 73 boiling point by an electTic liot-plate. The Gwathmey vapor apparatus was attached to this heater; compressed air was passed through the ether bottle, the resulting ether-vapor-air stream then passing through the water-bottle of the vapor-apparatus, and finally through the heater and the tube into which were inserted thermometers. Eeadings were made every five minutes for one hour and the room temperature was noted at the same time. The following table shows the results: TABLE 2 — Using Glass Air Condenser Attached to Heater Amount of ether taken, 4 ounces. Amount of ether used, 3 ounces. Compressed air flow, continuously through ether. Room temperature, 23.5° C. Temperature in Degrees Centigrade at Various Distances November 4, 1911 Time in minutes 5 10 15 20 25^ 30 35 40 45 50 55 60 From heater: At 10 cm.... 36 40.5 42 38.5 40 41 40 44 44.5 45 16 47 At 20 cm.... 27 33.5 34 32 33.5 33.5 33 35 35 34.5 34.5 35 At 30 cm.... 25 30.5 30 29 30.5 30 29 31 30.5 30.5 30 30 At 40 cm.... 24 28 28 28 28 28 27 29 29 29 29 29 At 50 cm 24 26.5 26 26 26.5 26 26 28 28 28 27.5 27.5 At 60 cm. .. 24 26 25.5 25 26 25.5 25.5 26.5 26.5 26.5 26.5 26.5 ' Eearrangement of flow. Boothby ^ has maintained that "warmed ether per se" possesses no merits over "cold ether," that is, not warmed. According to him, the concentration of the ether vapor in the air passing over or through the ether varies with the temperature of the liquid ether itself, that is, as the ether evaporates more or less rapidly the temperature of the liquid is lowered with a decrease in concentration of ether vapor in the effluent mixture from the vaporizer, hence the patient does not get enough ether. The specific heat of ether vapor is very small, consequently the mixture quickly acquires room temperature. Air, the volume of which per minute was determined by a Bohr meter, was passed over the surface of ether placed in a Wolff bottle, wherein the ether presented a surface area of about 50 sq. cm. The temperature of the liquid ether was noted with a thermometer immersed about 1.5 cm. in the ether. The tempera- ^ Discussion before the New York Society of Anesthetists, 1913. Copies of the curves were courteously provided by Dr. Boothby. U^5 CM II CM II / E it ^ A p- CO d; &y i / Q. a. f Q_ V H ■Jj — ■ — L — p2 , 3U09 .04 3 / M 1 / CM / / ^1 CM CM II II £ ' II I V ' u CD q: r/ <<; ?/ i ci &i r-e^ i> % HH ..^ V V >^ _I / y ^ ^ X' 7-= -— — ■ J3q;3 JO ;uoo jaj jaqi3 p -dijuax •uj|/\| jad j]y |o sj8;i-i i pa^sncqxg S| J3413 SB F addojg "c ^3 \, ^ CO \ ^ eg ^ o c :3 CM CM S a. i y CM II CM II UJ ^ Q- / E O" / LJ ■Jj / / CD c ce Q- y J c / Ci, F F H J CL ^ ' H H -^ X ■— - GENERAL PHYSIOLOGY OP INHALATION ANESTHESIA 75 ture of the air-ether mixture coming from tlie apparatus was noted in a Waller gas balance, which served to indicate tlie coinposiiioii of the m\x- 40 r ^|i!u30 Ha!20 /v / / ^ / "^ ''^-c ■at -E-th-c i ^ r Vap 'r in the A r O k Tcmf Tem . in E Lin i alanc ioom ! Con 23.2° tant i t 23. 2° V r \ ill f \ Lite ■3 of ; lir per Minu te TD O. "^ JTerry ■ of the_L E-t-h-e-r a. Ul 15 10 5 -5 -10 Minutes 10 20 30 40 50 50 70 80 90 100 110 120 Fig. 13d. — Boothby Curve. ture. The curves obtained by Boothby are given herewith, sufficiently labeled to be self-explanatory. In connection with Boothby's con- clusions the following facts demand con- sideration : (1) Ether given by the "vapor method" does not go, mixed with air or oxygen, first into a ballon or reservoir subsequently to be breathed by the pa- tient, but directly to the patient, hence it enters the air passages before it has had time to acquire room temperature. (See Authors' Experiments, p. G3.) (2) Ether administered in any way by inhalation eventually reaches body temperature in the lungs. The total shortage of heat is not taken from the entire surface of the lungs, but is local- ized in the bronchial passages, that is, there is local chilling or heating if the vapor be too hot. (3) Davis has shown clinically that very beneficial results are had even if the vapor be produced from cold ether, pro- vided it is subsequently warmed. (See Chapter on Administration, p. 67.) \ \ \ \ V \ c o \ V \ u It., np. i nBa \ ■ o "^ ■' Q. Te np. n Ro om = 2i (J> Lite ■s pe ■ Mir ute X I TJ s ^ O. \ H \ S XI \^ "5 DQ 5 10 15 20 25 30 35 40 Fig. 13e. — Boothby Curve. 76 ANESTHESIA From the preceding table it will be seen that ether vapor may be heated, and the heating maintained for any length of time and delivered to a patient as jjredetermined by the anesthetist. For instance, we see that at 60 cm. from the heater at the end of sixty minutes the tem- perature was three degrees C. higher than the room temperature. About the same amounts of ether and air were used in this experiment as are usual in practice. Air was passed through the ether and water-bottle of the vapor- apparatus without the heater and readings kept uj) for forty-five min- utes. The following table gives the result: TABLE 3 — Non-Warmed — Room Temperature Room temperature After 5 minutes 27.5° C. 28° C. After 10 minutes 27° 28° After 15 minutes 27.5° 28° After 20 minutes 27.5° 28° After 25 minutes 27.5° 28° After 30 minutes 27.5° 28° After 35 minutes 27° 27° After 40 minutes 27° 27° After 45 minutes 27° 27° From this table it will be seen that at the end of forty-five minutes the vapor was approximately sixteen degrees F. below blood temperature. The results show that ether vapor can be heated easily and inexpen- sively, and that it can be delivered to the patient at any desired tem- perature, within limits, by placing the heater or warming device at different distances from the patient's face. Effects of Moisture. — Since 1909, Gwathmey has employed warmed moist vapors for pulmonary anesthetics. Baskerville ^ has called atten- tion to the importance of moisture, among other factors which influence the course of anesthesia. "It has been shown,^' he says, "that the admin- istration of moist ether, free from aldehyd, at body temperature, is rarely followed by nausea (less than ten per cent), and the usual strain upon the kidneys is not observed." "Nitrous oxid, ether, and chloroform," he continues, "each exerts its specific physiological effect in producing anesthesia without asphyxia- tion, provided the respiratory and cardiac functions are approximately normal. This may be and is being accomplished by administering these gasified drugs with sufficient oxygen not to interfere seriously with the ^Baskerville: "The Chemistry of Anesthetics," Science, n. s., Aug. 11, 1911. GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA • 77 normal function of the hemoglobin of carrying oxygen to the capillaries, and sustaining cardiac stimulation, and by maintaining the usual con- centration of carbon dioxid in, and providing its regular elimination from, the blood; for it is the respiratory stimulant (Yaiidall Hender- son). Other factors involved are temperature and moisture. The anes- thetics are carried into the system at body temperature. This may be and is being accomplished by warming, and, in the case of ether and anesthetic chloroform, by passing the vapor through heated water, which, at body temperature, not only removes the oxidation products, but sat- urates the gas with moisture (Gwathmey method). The osmotic action of the alveolar cells is thus affected only to the extent of the density of the gases introduced into the lungs, and not, as normally is the case, by temperature (always lower) and desiccation as well." Briining,^ j&nding compressed air relatively much more harmful to the lungs than pure oxygen, or air in the Geppert apparatus, instituted experiments to determine the factors which cause the difference in effect. Differences in the temperature could not, in his oiDinion, be responsible, as repeated measurements always showed 25° to 30° in all the gases, uniformly. For the same reason, the strength of the air current could not be responsible. The remaining factor was the content in moisture of the different gases. The oxygen and the air from the steel cylinders had only a relative humidity of 10-15 per cent. These values are so low that the sojourn in such dry air would normally be harmful for man and might lead to pneumonia. We feel most comfortable in air which contains between 40- 60 per cent moisture. Inspiration or Compressed Air With Water Vapor. — In a series of experiments upon mice, different degrees of moisture were obtained by allowing water to drip into the air stream. The desired humidity was produced in such a way that water was poured into the ether-flask of the Eoth-Drager apparatus, with a regulated outflow of the water, so that, after some practice, the gas-mixture would be maintained fairly constant at the desired humidity. (See Table 4, page 78.) The table shows that the lungs presented nothing pathological, with moisture contents of the air from 50-70 per cent. Even after three breathing periods no changes were found. But when the moisture con- tents were diminished below 40 per cent, or increased to 100 per cent, hemorrhages at once made their appearance. As the air in Geppert's apparatus contains approximately 95 per cent relative moisture, the occurrence of slight pulmonary lesions is readily understood. The entire ^ Briining, A. : " Studien zur Narkosenfrage, ins besondere liber die An- wendung von Sauerstoff und komprimierter Luft, " Deut. Z. Cliir., 1911-12, 113, 532. 78 • ANESTHESIA TABLE 4 — Inspiration of Compressed Air With Water Vapor Mouse No. Duration of exp. Time to sacrifice or second exp. Second exp. Time to sacrifice Macroscopical lung findings Moisture contents of air 36 hours at once Nothing pathological 70% 45 IM hours at once . Some hyperemia, otherwise normal 35% 41 2 hours at once Normal appearance 55% 42 2 hours 7 hours Some hyperemia, otherwise normal 55% 37 hours 19K hours 2 hours at once Nothing pathological 70.65% 38 hours 193^ hours 2 hours 22 hours free 3d experiment, ^ hour, killed at once. Lungs normal 70.65 + % 46 hours at once Marked hyperemia, some hemorrhages 100% experimental series justifies the conclusion that too much dryness and too much moisture are injurious for the lungs ; but when these extremes are avoided, oxygen, compressed air, and the Geppert apparatus can be equally recommended. A later series of experiments showed similar pulmonary changes from artificially dried air, as after the breathing of air that had been com- pressed; therefore, the cause of the hemorrhages cannot be referable to any abnormal composition of the air in the steel cylinders. It still remains to be shown why the lungs are less injured by oxygen, although it has only a relative moisture content of 10-15 per cent, than by the equally dry air; and also why the dryness as such can act harm- fully. Injuries through very dry air are explained by Briining as follows : The alveolar epithelia are lined with a thin layer of water, which is derived from the blood, and by its constant evaporation invests the GENERAL PHYSIOLOGY OE INHALATION ANESTHESIA 79 expired air with its high content of moisture. In this thin hiyor, oxy- gen is dissolved and is carried from here hy diffusion to tlic hlood corpuscles. When the moisture contents of the inspired air are ahiior- mally low, the water evaporates very rapidly, the capillaries — which are exposed for a large part of their circumference — dry out, and permit the blood corpuscles to pass between them. In addition, the secretion- pressure for oxygen drops, through the lesion of the endothelia, and the organism reacts by an increased blood supply — hyperemia — in order to take up the same quantity of oxygen through an increased surface. In the further course, inflammatory manifestations on the bronchi make their appearance. The slight bloody extravasates, on breathing of pure oxygen, are interpreted by Brlining as a chemical injury. The passage through a dried-out cell being necessarily hindered, the oxygen remains for a longer time in contact with the protoplasm; or the cell must exert an increased activity, in order to accomplish the same functional results. Consequently, there are over-stimulation and over-taxation of the cell. On breathing an air saturated with water-vapor, the evaporation of the alveolar moisture proceeds more slowly, the water-layer at the walls is likely to be thicker and to stimulate the cells by its constant oxygen- contents. The secretion-pressure of the endothelia is normally subject to constant fluctuations, in the opinion of Briining, corresponding to inspiration and expiration, so that the cellular protoplasm regularly enjoys a brief rest. The slightness of the pulmonary changes, on the breathing of pure oxygen, is attributed by Briining to the increased oxygen partial pres- sure, which facilitates diffusion and secretion. Briining concluded, from his experiments, that, in the brief time of a general anesthesia, injury to the lungs is to be feared only under em- ployment of compressed air from the steel cylinders, and that this can be avoided by moistening the air to about 50 per cent. The examination of the lungs, after the inhalation of the different gases, showed very considerable difference. After the inspiration of compressed air, the lungs of mice invariably showed extensive hemor- rhages and bronchitic symptoms, which were especially evident after long duration of the experiment, or several repetitions. The air in Gep- pert's apparatus and oxygen have a similar effect, but to a much less degree. The lesions are dependent upon the relative moisture of the air, and can be avoided by moistening the inspiration air with water vapor, up to 50-80 per cent. Too high a vapor-saturation acts in the same sense as too much dryness. The absence of grave lesions in oxygen- breathing, in spite of low moisture, is referable to specific properties of the oxygen. Briining's experiments led to the following practical conclusions : (1) General anesthesia by means of the Eoth-Drager apparatus. 80 ANESTHESIA under utilization of oxygen, is preferable to general anesthesia under employment of compressed air, unless the moisture of the air is artifi- cially increased to 50 per cent. (2) General anesthesia with oxygen is equivalent to general anes- thesia by means of the Geppert apparatus. (3) In the accidents of general anesthesia, artificial respiration alone is always efficient for the introduction of enough oxygen into the body; the breathing of pure oxygen offers no advantages. (4) The majority of the advantages, claimed for oxygen, are only due to the more accurate dosage by means of the modern anesthetic apparatus. Combining Oxygen with the Agent. — In 1904, experiments were conducted (J. T. G.)^ to determine the value of oxygen, as compared with atmospheric air, in combination with different anesthetic agents, attention having been particularly directed to the subject by certain statements made by Hewitt. With reference to nitrous oxid Hewitt says : "It is now established beyond all doubt that, by employing certain percentages of atmospheric air with nitrous oxid, a better form of anesthesia can be obtained than with the undiluted gas, and that, by using oxygen instead of atmospheric air, a still better form of anesthesia is obtainable.'^ Concerning chloroform, however, Hewitt's views are not so favorable : "It is doubtful whether there is any great advantage in the addition of oxygen to atmospheric air during the administration of chloroform, save perhaps in cases in which much respiratory difficulty is present, and in these cases the use of any tightly fitting inhaling apparatus would almost certainly neutralize the theoretical advantages of using oxygen." Eeasons for Using Oxygen.— The advocacy of the combination of oxygen with inhalation anesthetics is based largely upon the experiments of Priestley, Demarquay, Eichet, Paul Bert, and others, and upon the clinical observations of Andrews, of Chicago, with nitrous oxid, and of Neudorfer, of Vienna, with chloroform. The reason for giving oxygen with nitrous oxid is explained by Hewitt " in the following manner : "A mixture of 40 per cent of air and GO per cent of nitrous oxid would contain about 8 per cent of oxygen and 32 per cent of nitrogen; and although the 8 per cent of oxygen would be sufficient to nearly or completely preserve the natural color of the patient's face, and to suppress clonic muscular spasm, the 60 per cent of nitrous oxid would be insufficient to produce tranquil anesthesia. If, however, instead of using air for oxygenating purposes, we employ oxygen, we shall be able to replace the 32 per cent of useless ^Gwathmey, J. T. : "Experiments to Determine the Value of Oxygen in Combination with the Different General Anesthetics," Med. Bee, Nov. 19, 1904. = Hewitt: " Anesthetics, " 4th ed., 311. GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 81 nitrogen by a corresponding quantity of useful nitrous ox id, and the proportion of the latter will now rise to 92 per cent." From this it will be seen that there is a physiological basis for the combination of oxygen with nitrous oxid. Clinical experience bears out the theoretical calculations. The ground for using oxygen with chloroform or the "C.E. - mix- ture," ether, or ethyl chlorid, is as well founded, theoretically and clin- ically, as is that of its combination with nitrous oxid. Normally for every volume of inspired air, 4.8 per cent of oxygen is abstracted, 4.3 per cent of carbon dioxid being substituted. During anesthesia the blood becomes more and more venous from an obstruction to the entrance of p,ir into the lungs, and from the blood failing to take from the air its usual supply of oxygen. Asphyxia is produced more by the diminution of oxygen than by the increased amount of carbon dioxid. According to Patton,'^ Eumph found a decrease of 40 per cent of carbon dioxid eliminated in the respiratory exchanges, and Eichet found a decrease of 50 per cent in the elimination of carbon dioxid in chloralized dogs. Bert's experiments with chloroform show a progressive diminution in oxygen absorbed, and of carbon dioxid given off. Lorrain Smith has shown that dyspnea from changes in the gaseous composition of the blood may be due to a deficiency of oxygen. Eichet states that blood which contains an anesthetic in solution preserves, when shaken with ether, its full ability for fixing oxygen. Irregular forms of breathing may also occur from too little oxygen, as in the closed administration of volatile agents; or, from carbon dioxid dyspnea, as in rebreathing during the administration. The experiments of Priestley and others, of placing small animals under two different receivers, one filled with oxygen and the other with air, showed that those under the oxygen receiver survived twice as long as the others ; also, that the death of birds in the oxygen was not accom- panied by convulsions as was that of birds that died in the air ; further- more, that the heart retained its irritability for several hours when death took place in oxygen, Demarquay ^ immersed two kittens in water and kept them there until they had lost consciousness. One had previously been confined for twenty minutes in a glass case, containing two parts of oxygen and one of air, and the other had breathed only atmospheric air. On removing them from the water there was only a slight movement of the lower jaw. At the end of five minutes and a half, the superoxygenated kitten ^Patton, Joseph M. : "Anesthesia and Anesthetics," 1903. ^ Demarquay, J. N. : " Essay on Medical Pneumatology : Physiological, Clinical, and Therapeutic Investigation of the Gases," Translated by Samuel S. Wallian, A.M., M.D., 1889. 82 . ANESTHESIA arose, totteringly walked around, and made an uneventful recovery. The other partially recovered at the end of fifteen minutes, but died the next day. These experiments were repeated a number of times, and always with the same result. The above experiments, illustrating the value of oxygen as compared to air, have been practically paralleled by Gwathmey. Eegardless of the anesthetic used, animals have lived twice as long with oxygen as with air. With oxygen the heart continued to beat long after respiration ceased. It may be added here that the heart always continued to beat a variable length of time after respiration ceased, whether air or oxygen was used, and with all anesthetics. Greater success in reviving them after cessation of respiratory and cardiac activity has come with the use of oxygen than with air. The after-effects produced upon animals have been carefully studied. Inasmuch as oxygen is constantly employed clinically, with both chloro- form and ether, it may be stated positively that the after-effects are reduced to a minimum. Experiments with Animals. — In the experiments conducted by Gwathmey a closed mask with an expiratory valve, with the light rubber bag just behind the mask, was used. This animal mask was a cone-shaped brass cylinder 3^/2 inches in diameter at the base and 1% inches at the apex. Over the base, or open end, were stretched two thicknesses of thin rubber, fastened around the margin of the cone by a rubber band. A small opening 1^ inches in diameter was cut in the center, into which the animal's nose was placed. The technique in each instance was as nearly as possible the same, the same amount of anes- thetic being used in each experiment, and the flow of air and oxygen being regulated. To make these experiments as accurate as possible, over one hundred animals were killed, and the average time recorded. It has not been deemed necessary to enter into details of the exact weight, age, size, and physical condition of each animal. It may be said, however, that ani- mals as nearly alike as possible in all essential respects were selected for each comparison. The results, in detail, as will be seen from the tables on pages 84 and 85, varied in accordance with the individual characteristics and conditions ; as a whole, they confirmed the claim that the use of oxygen in connection wi.th any form of anesthetic practically eliminates the percentage of danger which has hitherto been recognized as inseparable from the practice of anesthesia. In order to determine the difference in toxicity of the drugs used, the time was taken from the application of the mask to the stoppage of the heart. As the toxic effects came on so rapidly, observations on the pulse, respiration, and blood pressure were of little value. GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 83 Twenty-six animals were killed with chloroform and air, the average time being nine minutes; the shortest time, three minutes; the longest, seventeen minutes. Thirty-eight animals were killed with chloroform and oxygen, the average time being twenty-one minutes; the shortest time, five minutes; and the longest, one hour and a half. (See p. 84.) With ether and air twelve were killed, the average time being nine- teen minutes, the shortest fifteen, and the longest thirty-three minutes. Seven were killed with the same anesthetic and oxygen, the average time being thirty-five minutes, the shortest twenty-five minutes, and the long- est one hour. (See p. 85.) With one part of chloroform and two parts of ether, thirteen animals were killed, six with air and seven with oxygen. The average time with air was nineteen minutes ; with oxygen, thirty-five minutes. The short- est time with this mixture and air was fifteen minutes ; the longest time, thirty minutes. The shortest time with oxygen was sixteen minutes; the longest, one hour and ten minutes. (See p. 85.) From the above it will be seen that chloroform with oxygen is safer than chloroform with air, and is also safer than any of the other general anesthetics with air. This means that, instead of giving a very high mortality, chloroform with oxygen is as safe as ether with air. From the above experiments and clinical observations it may be deduced that oxygen increases the value of all anesthetics in rendering their administration safer to the patient without decreasing the anes- thetic quality. In a recent paper Briining ^ discusses the value of oxygen employed in connection with narcotics. He states that oxygen alone will not account for the improved narcosis witnessed in the administration of anesthetics with perfected apparatus. He attributes this to the exact and equal dosage, and maintains that compressed air is equally useful if the moisture of the lungs is artificially increased to 50 per cent. (See p. 86.) In accidents in narcosis, according to Briining, artificial respiration alone is always sufficient to introduce oxygen into the body. Pure oxy- gen inhalation offers no advantage. The smaller proportion of anesthetic needed when oxygen is employed he attributes solely to the improved dosage facilities with the Eoth-Drager apparatus. The minimizing of the after-effects, such as headache, vomiting, etc., he attributes to the diminished amount of chloroform employed. The employment of oxygen inhalation after narcosis is of no special value, as deep breathing and a thorough ventilation of the lungs promote the more rapid elimination of the anesthetic. Briining states that a patient with rosy lips and a pink appearance might suddenly become asphyxiated, as saturation with chloroform ^ Briining : Loc. cit. 84 ANESTHESIA TABLE 5. The figures in the first column indicate the number of the experiment; the second column, the number of minutes required to kill. 43^ Chloroform 1 With Air 1 43^ 2 3 3 W2 4 7 5 4 6 4 7 3K 8 7H 9 9 10 53^ 11 7 12 10 13 6 14 9 15 10 16 W2 17 103^ 18 10 19 10 20 17 21 16 22 13 23 16 24 11 25 12 26 12 2323/^ total; ?.94 average. With Oxygen 1 26 2 5 3 10 4 5^ 5 30 6 40 7 28 8 13 9 5 10 8 11 15 12 17 13 30 14 30 15 13 16 18 17 14 18 30 19 163^ 20 37 21 28M 22 33 23 8 24 103^ 25 10 26 103^ 27 18 28 7 29 183^ 30 413^ 31 13 32 26 33 73^ 34 90 35 14 36 26 37 23 38 331^ 809K total; 21.3 average GENERAL PSYCHOLOGY OF INHALATION ANESTHESIA 85 1 2 3 4 5 6 7 8 9 10 11 12 With Air 15 Ether 18 '.'.'.'.'.'. " 27 " 15 " 33 " 16 " 18 " 21 " 16 " 9 " 18M " 28M " 235 total; 19 average. With Air Mixed Chloroform and Ether (1 :2) 15 30 lOM 15 17 6 30 With Oxygen 1 25 2 29K 3 33J^ 4 34 5 27 6 40 7 QVA 250H total; 35 average. With Oxygen 40 16 70 37 42 22 28^ 117H total; 19 average. With Air 3^ 21 Anesthol 2 26 ■.'.'. " 3 10 " 57 total; 19 average. 2551^ total; 36 average. With Oxygen 1 38 2 14H 3 74 126 total; 42 average. "With Summary With Air . 0^>f ^ 9 Chloroform 1 21 19 Chloroform and Ether 2 35 Ether 3 35 12 19 Anesthol ^ 42 86 ANESTHESIA would not change the color of the blood. He claims that more oxygen is set free in the plasma of the blood, and that the color depends only upon its richness in oxygen and not upon its carbon dioxid. Znntz ^ holds that aniinals die as soon under oxygen-chloroform as under air-chloro- form. In chloroform poisoning, according to Briining, the first thing to do is to reduce the concentration of poison in the blood and to eliminate it from the body. To do this, the circulation must be maintained so that the hypersaturated blood may go through the lungs and be purified. This is best accomplished by radical, artificial breathing, thus securing a thorough expansion of the lungs. In this way, so much oxygen is introduced into the lungs that the inhalation of concentrated oxygen is unnecessary. Vidal ^ asserts that in primary disturbances of the respira- tion only artificial breathing is necessary, as, owing to the blood becom- ing rich in oxygen, eupnea, which delays the excretion of chloroform, occurs. In treating accidents in narcosis a suggestion is made that oxygen might exercise a directly injurious chemical action on the body cells. Briining quotes Paul Bert as stating that animals die when exposed to a hyper-pressure of 3-4 atmospheres of pure oxygen. As animals, on inhalation of ordinary air, died only on a hyper-pressure of 15 to 20 atmospheres, he thought the danger lay not in the pressure, but in the oxygen. Briining makes the peculiar statement that, from his experimenta- tion, the administration of oxygen after the narcosis only delays the awakening, inasmuch as it never hastens the elimination of chloroform. Furthermore, in his ojDinion, it is no antidote to chloroform in narcosis accidents. Deep, free breathing is always sufficient to eliminate the chloroform from the system. The difference in the results of Briining's experiments and those of Gwathmey can be explained only by the employment of an entirely dif- ferent technique and difi:erent apparatus under different conditions of climate. In Gwathmey's experiments, results were obtained by elim- inating as far as possible every factor that might tend to confuse. Eebreathing, as advocated by Gatch, was used constantly, both with oxygen and compressed air. There is not the slightest question but that, under proper conditions, oxygen, in a very great measure, prevents poisoning, especially in chloroform or ether narcosis. Miiller's ^ experimental findings are divided into three groups, namely chloroform-oxygen narcosis; ether-oxygen narcosis; and com- bined narcosis, the latter being subdivided according to sequence, ^Zuntz: Berl. Tclin. Woch., 1901, No. 20. = Vidal: Zentr. Cliir., 1911, No. 11. ^ Miiller, B. : " Ueber den Einfluss der Gange mischnarkosen auf die innereii Organe," Arch. f. Min. Chir., 1905, 71, 420. GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 87 namely, chloroform-ether-oxygcn narcosis and ether-chloroi'orm-oxygen narcosis. Chloroform-oxygen narcosis diminishes the blood pressure, which drops constantly from the beginning of tolerance to the end, rising again when the patient awakens. The diminution of the blood pressure is considerably less in chloroform-oxygen narcosis than in simple chloro- form narcosis. The height of the blood pressure never drops so low below the normal blood pressure as in simple chloroform narcosis, and the course of the oxygen-mixture narcosis is of uniform appearance. But remissions are not altogether absent, and the chloroform effect can there- fore not be entirely overcome. The number of respirations undergoes a greater diminution with chloroform alone than with the oxygen-mixture narcosis, in which it approximates the normal standard. Concerning the effect of the oxygen narcosis upon the internal organs, the advantage of the addition of oxygen to chloroform consists in the removal of the carbon dioxid and in its substitution by oxygen, which induces a greater power of resistance on the part of the individual cells. The fatty changes of the cells, as well as the effect upon the heart, are not so severe in mixed as in simple chloroform narcosis. The mixed narcosis also involves a considerable saving of chloroform. In the oxygen-ether narcosis no depressive effect upon the blood pressure was demonstrable. The level of the blood pressure was always above normal, so that the blood pressure was invariably increased, exactly the opposite to chloroform-oxygen narcosis. Ether-oxygen acts upon the internal organs in an analogous fashion to ether, but the changes are less considerable, especially the salivation and fatty metamorphosis. The difference is due to similar factors to those in chloroform-oxygen inhalation, namely, the lessened consumption of ether, the supply of oxygen, and the prevention of carbon dioxid intoxication. Ether-oxygen narcosis possesses less narcotic power as compared to simple ether narcosis, especially in resistant individuals, habitual users of al- cohol, etc. Combined oxygen inhalation, with ether and chloroform, is utilized for the avoidance of the disadvantages of these two methods of narcosis; it diminishes the toxic effects of ether as well as of chloroform, but requires accurate dosage, careful observation of the patient, and a knowl- edge of the indications and contraindications for the individual anes- thetic agents. The effects of ether, for example, are merely diminished, but still present, so that certain dangers are involved in the narcosis if the patient is predisposed. Therefore, definite indications must always be present for this narcosis, for there are patients who are predisposed to a toxic effect of ether and unable to tolerate this narcosis. Ether-oxygen narcosis furthermore possesses less narcotic power than simple ether nar- cosis, and this is especially important in resistant individuals, such as 88 ANESTHESIA neurasthenics and habitual users of alcohol, who in many cases cannot be brought under the influence of ether-oxygen narcosis. A reduced nar- cotic power is also frequently noted in chloroform-oxygen narcosis, so that it is difficult or impossible to narcotize alcoholic individuals. In order to avoid the disadvantages of chloroform-oxygen narcosis as well as of ether-oxygen narcosis, a combination of the two narcoses has been created in the form of combined oxygen narcosis, which is subdivided into chloroform-ether-oxygen narcosis and ether-chloroform-oxygen nar- cosis. By means of these combined narcoses the dangers and disadvan- tages of inhalation narcosis are much reduced. The favorable effects of these narcoses are due to diminution of the toxic action of ether as well as chloroform. Miiller ^ investigated the fatty changes of the vital parenchymatous internal organs in animals after simple and mixed narcoses. It was found that any narcosis gives rise to a more or less well-marked incipient fatty metamorphosis in the internal organs. The change in the kidney is frequently not marked enough for albuminuria to appear, but some alteration of the epithelia is present after all narcoses. This incipient fatty metamorphosis, which does not attack all cells at once, promptly subsides again. An existing fatty metamorphosis, such as is caused, for example, by a preceding narcosis, becomes seriously aggravated by a re- peated inhalation of narcotic agents. It makes no difference what anes- thetic is used; chloroform, chloral hydrate, and ethyl bromid have the most energetic action in this respect; the last named agent being alto- gether useless for prolonged narcosis. Ether acts in a general way less strongly upon the heart and brain, but, after several narcoses with ether, fatty changes are likewise found in these organs. Each prolonged ether narcosis is followed by small pneumonic foci in the lungs, with mucus in the alveoli, collection of blood corpuscles in the alveoli, and round cell in- filtration in the surrounding tissue. These lung changes are of slight degree with chloroform. On the other hand, the liver and the kidney are affected less by ether than by chloroform. In a general way, there is a certain uniformity about the injurious effects of the various nar- .cotics, except graded differences in the intensity of the action. Mixtures of chloroform and ether were found to be by no means better anesthetics, but rather possessed worse properties. The experiments showed that any mixture which contained chloroform did not act very differently from a pure chloroform narcosis. Mixed ether narcoses were followed, like the pure ether narcoses, by pneumonias of the above-described type. The practical application of these findings consists in the best possi- ble abbreviation of the narcosis; the avoidance of repeated narcosis ^Miiller, B.: "Ueber Fettmetamorphose in den inneren parenchymatosen lebenswichtigen Organen nach einfachen und Misch-Narkosen. " Arch. f. Min. Chir., 1905, 75, 896. Fig. 14. — Oxygen Passing through Rubber Ccil Immersed in Hot Water (Service of Dr. Bainbridge) . Fig. 15. —Intra-abdominal Administration of Oxygen in Case of Intestinal Adhesions. 90 ANESTHESIA within three to six days; and the examination of the organs before each narcosis, as to a preexisting fatty metamorphosis. Certain aifections are a strict contra-indication against any narcosis, especially fatty meta- morphosis in the heart, kidneys, and liver. The Influence upon Anesthesia of Oxygen Intra-abdominally Ad- ministered. — It is not proposed in the present volume to consider surgical subjects such as may re- late to or modify the ad- ministration of a n e s - thetics. However, it is of importance to note the effect upon anesthesia of oxygen administered in- tra-abdominally, accord- ing to the method of Bain- bridge,^ who instituted, for purposes not connected with anesthesia, a series of animal experiments with oxygen and air, which verified, in a re- markable manner, our ex- periments with oxygen and the different anes- thetics. In a series of experi- ments to determine the difference between oxygen and air, oxygen was intro- duced into the abdomen following the technique as described upon human beings. It was found that oxygen was completely absorbed in alk cases left undisturbed for seventy-two hours. There was a slight increase in pulse rate and respiration, also a slight rise in blood pressure. The effect upon the degree of anesthesia was marked, the animal showing a tendency to recover almost immedi- ately from the influence of the anesthetic. In cases where the anesthesia was profound, reflexes quickly became active. Animals into which the oxygen had been introduced were able to stand up from two to ten minutes after the discontinuance of the anesthetic. All reactions were more prompt when warmed .oxygen was used instead of oxj^gen at normal temperature. The dark blood was changed to scarlet. In no ^ Bainbridge, W. S. : Annals of Surgery, March, 1909 ; N. Y. J. Med., June, 1908; N. Y. Med. J., Apr., 1909. FiG.^ 16. — Suturing op the Peritoneum. Continu- ous stitch to inserted tube; purse-string stitch (1) encircling tube. GENERAL PHYSIOLOGY OE INHALATION ANESTHESIA 91 case was there macroscopic evidence that oxygen was an irritant to the peritoneum or any of the abdominal viscera. It was also found that oxygen stimulated intestinal peristalsis. When air was introduced instead of oxygen, the pulse, respiration, and blood pressure were particularly influenced, and the degree of anes- FiG. 17. — Aponeurosis United with Interrupted Sutures, the Muscle Having Been Previously Sutured. (1) Untied ends of peritoneal purse-string; (2) Untied suture through aponeurosis, passing halfway around tube. thesia was not affected. The time required for recovery after the anes- thetic agent had been discontinued was from fifteen to twenty-five minutes. In the abdominal administration of oxygen Bainbridge employs a gas containing 94-97 per cent oxygen. The gas is warmed to a tem- perature of 90°-100° F., by passing it through a rubber tube from the tank in which it is compressed into a wash bottle filled with hot water. From this bottle the partially warmed gas passes through the exit tube. This long exit tube is again connected to a piece of glass tubing, and to this, in turn, is attached a piece of sterile rubber tube, through which the gas is introduced into the abdominal cavity. (Figs 14 and 15.) Animal experiments and clinical experience in a large number of 92 ANESTHESIA cases have proven that oxygen can be safely administered intra-abdom- inally, that it lessens shock, controls hemorrhage from small vessels, lessens the degree of cyanosis, nausea, and vomiting, prevents the for- mation of adhesions, and stimulates to such a degree that more anes- thetic is necessary in order to keep the patient anesthetized until the completion of the operation. The technique of closing the wound and withdrawing the rubber tube, so as to prevent the leakage of oxygen, either into the tissues or into the surrounding atmosphere, is shown in Figures 16, 17, 18, and 19. Preceding the Administration with Oil of Bitter Orange Peel. — A procedure which exerts a striking influence upon the course of anes- thesia is the preliminary adminis- tration by inhalation of oil of orange (25 per cent oil of bitter orange peel, U. S. P., with 75 per cent of alcohol, U. S. P.). Gwathmey,^ who first employed this method, had long been in the habit of preceding the anesthesia by the administration of a one per cent vapor of cologne or whiskey, the agent being placed in one of the bottles of his three-bottle vapor ap- paratus (see illustration, p. 225). Later he adopted oil of bergamot or terpineol ^ for the purpose of mask- ing the odor of ether vapor. (See Chapter VIII.) Finding the induction period of anesthesia thus deprived of its ter- rors for many patients, particularly for nervous women and frightened children, the subject lapsing quietly into unconsciousness when the anes- thetic vapor was turned on, a search was instituted for a substance with a more penetrating yet none the less agreeable odor, which could be vaporized and utilized as a preliminary to ether or other inhalation anesthetic agent. With this object in view, the authors experimented with a number of ^Gwathmey: "The Vapor Method of Anesthesia," Med. Bee, Oct. 14, 1905. ^Gwathmey: Terpineol ("lilaeine") serves to mask the odor of ether vapor, and is a respiratory antiseptic, but, like oil of sweet orange, is less satisfactory than oil of bitter orange peel, because of its very sweet odor. Fig. 18. — Superficial Fascia United. (1) Untied peritoneal purse-string; (2) Untied aponeurosis suture. GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 93 odoriferous substances.^ From the table (page 94), by Passy,^ quoted by Tigerstedt,^ and rearranged here in the sequence of penetrating power, it will be seen that other odorifer- ous substances exceed oil of orange in penetrative power. To these, however, some patients might find objection, whereas to the delightful odor of oil of bitter orange peel it is hardly likely that anyone would object.* The table shows how many milli- grams of odorous substances, respective- ly, must be contained in one liter of air in order to produce a barely perceptible olfactory sensation. The list illustrates the functional capacity of the human ol- factory organ in regard to quantity. Zwaademaker,^ using the olfactom- eter, noticed that in the case of certain odoriferous substances the threshold, or very first beginning, of perception takes on a high value, under increasing con- centration, after a certain optimum has been reached. With the above facts in mind, Gwathmey employed oil of bitter orange peel in alcoholic solution, first using it by the drop method with ether. He found that in this way the odor of ether was completely masked, not only for the patient but for the occupants of the operating room as well. The patient passed into the stage of surgical anesthesia as one dropping into a profound sleep. There was no stage of excitement, the nausea and vomiting being materially reduced. The Fig. 19. — Tube Withdrawn; Peri- toneal Purse-string Tied; Knot Beneath Aponeurosis. (3) Aponeurosis suture. Figure illustrates practicability of plac- ing skin-stitches while tube re- mains in the abdomen. ^Nussbaum {Rundschau, 1888, 759) found that the odor of chloroform vapor might be masked by means of oil of cloves. In the experiments of the authors, the masking agents tried (terpineol, oil of bergamot, oil of patchouli, oil of lemon, orange, etc.) were superimposed upon water at 37° C, and the anesthetic vapor was then passed through. - Passy : ' ' Forme periodique du pouvoir odorant dans la serie grasse, ' ' Compt. rend. Acad. d. Sciences, 1893, 116, 1007. "Tigerstedt: "Lehrbuch der Physiologie des Menschen," 1902, f, 132. * Eulimen, a pure limonene (density, 0.850 at 15° C. ; boiling point, 175° C), prepared according to a patented process (D. R.-P. 204, 163), has been proposed as an addition to narcotic mixtures ("Riedel's Mentor," 1911, 152). ° Zwaademaker, H. : " Die Physiologie des Geruches, ' ' Leipsic, 1895. 94 ANESTHESIA TABLE 6. Milligrams per liter of air Mint leaves {Folia Menthce) . 0000005 — . 00001 Essence of Wintergreen . 000005 — . 0004 Orange essence 0.00005 —0.001 Ether 0.0005 —0.004 Camphor . 005 — Natural musk 0.01 —0.1 entire administration progressed smoothly, and the patient recovered from the anesthetic with none of the after-effects so frequently noted with ether.^ Woolsey, of Brooklyn, developed and perfected the method of employ- ing the oil of orange-ether sequence by the closed method with the three- bottle vapor inhaler. He has a record of over 200 cases. He uses it wherever the nitrous oxid-ether sequence is indicated and prefers it to the latter method. It is unquestionably of inestimable value, especially where the transportation back and forth of the nitrous oxid cylinders is a matter of consideration. The technique is as follows : ^ The water bottle is filled with the usual amount of water, namely, 3^ to 3 ounces. A solution of oil of orange, of the composition described, in one- to two-dram quantity, is placed in the water. Ether (four to six drams) is placed in the chloroform bottle, which receptacle is sur- rounded by lukewarm water. The usual quantity of ether (4 ounces) * French has used the drop method of oil of orange-ether in over 50 cases ; he states: "One of the most important and valuable recent contributions to anes- thesia methods is the ability to omit, or bridge, the second stage, or stage of excitement, and, judging by the results obtained, we are deeply impressed with the desirability of attaining narcosis without struggle. This can, without doubt, be accomplished, in the period of induction, with nitrous oxid; but, in our judgment, it can be done with greater ease and certainty with the essence of orange. It unquestionably requires a large experience with the administration of nitrous oxid to enable one to dovetail it so accurately with the ether which follows that the stage of excitement will be eliminated. It can, however, be done, and when done successfully, if all other things are equal, we can safely predict the best prospect for the operation and the best condition during recovery. The. remarkable effects of the oil of orange as a preliminary to ether have been dem- onstrated in our clinic, and have proved to our satisfaction that, with it, the ad- ministration of ether is made far less disagreeable and that it greatly assists in the reduction of shock by bridging the stage of excitement. We have used it repeatedly with perfect success, the patients sinking into complete anesthesia as a child falls to sleep. Our observations thus far have brought the belief that an anesthesia conducted in this way is a contributive factor in reducing hemorrhage, also in reducing the quantity of the anesthetic and in shortening and modify- ing the anesthetic after-effects." French, Thomas E. : "Nitrous Oxid, Es- sence of Orange, Ether, and Sequestration in General Anesthesia," N. Y. Med. J., May 24, 1913. *See also "Vapor Method of Anesthesia." GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 95 is placed in the ether bottle. The index is turned to "Air/' and the bag is filled with the air pumped through the water bottle, which con- tains the oil of orange. The mask is placed upon the patient's face, and the patient breathes back and forth in the bag. The air is pumped vigorously so as to keep the bag two-thirds full at all times. The index is turned gradually toward "Chloroform," the receptacle in which the four to six drams of ether are placed. The patient is now getting a very small amount of ether, which is apparently imperceptible. The index is gradually turned to full "Chloroform," the patient getting more and more of the mild attenuated ether vapor. If, at this time, the patient coughs, sneezes, or swallows, or shows in any way that he perceives the ether, the index is immediately turned back to "Air." The same pro- cedure is repeated until the index reaches full "Chloroform." When this is accomplished the index is turned back to air again and gradually turned toward "Ether." The expiratory valve is, at all times, only slightly open. The bag remains moderately distended, a slight positive pressure being a decided advantage in some cases, the expiratory valve permitting a continuous but small escape of air. The patient will now be found to be in a state of full surgical anesthesia, the average time required to reach this stage being four and one-half minutes. Anes- thesia is maintained with the index turned for one-eighth to one-quarter of an inch from air, but between "air" and "ether," constant pumping being continued at all times. The breathing, as a rule, is quiet and regular, approximating the breathing in chloroform anesthesia more nearly than that usually seen with ether. The lid reflex is absent, the eyeballs are rolling, but the patient is sufficiently relaxed for all surgical operations. The usual amount of ether used with this method is two or three ounces for the first hour and one ounce for the second. The after- effects are usually conspicuous by their absence. The patient goes under in practically the same way as with a good nitrous oxid-ether sequence. There is no struggling or other indication of the seco7id stage. The pulse is normal, the color reflex good, and there is no disturbing mucous rale. The physiological basis for the beneficial effect of oil of orange in the administration of inhalation anesthetics may be found in the pre- vention of reflex stimulation, by the anesthetic agent, of certain sensory nerves. Dastre ^ attributed early syncope to reflex stimulation of the pneumogastric and trigeminal nerves, particularly the sensory branches supplying the nasal mucous membrane and the larynx. Embley ^ has also emphasized the part played by the increased excitability of the vagus mechanism, particularly during the early part of the administra- tion. In his inhalation experiments Embley found that failure of respiration is mainly due to fall in blood pressure. With good blood ^"Les anesthetiques, " Paris, 1901, 104-109. == Embley: Brit. Med. J., April 5, 12, 19, 1902. 96 ANESTHESIA pressure, failure of respiration (his experiments concerned chloroform) is practically impossible. Eestoration of respiration is dependent upon restoration of blood pressure. The chances of dangerous vagus inhibi- tion aTe greatly increased by imperfect respiration. From these findings it would seem fair to assume that any factor which prevents undue reflex inhibition of the nervous mechanism of respiration and which, by its stimulation of the respiratory center, pre- vents fall in blood pressure, will have a beneficial influence upon the course of the anesthesia. The oil of orange seems to exert this bene- ficial influence by dulling the sense of smell to such an extent that the odor of the anesthetic agent is not noticeable during the administration. It has been determined by our laboratory experiments upon guinea-pigs that the oil of orange exhibits no pronounced anesthetic effect upon these animals. The exact nature of its physiological action is, therefore, yet to be determined. The smoothness of the anesthesia seems to the authors to be depend- ent upon the power of oil of orange to obtund the olfactory nerve to such an extent that the odor of the ether vapor is not noticeablfe. This view has not been verified by laboratory experimentation, however. Concerning this "Mystery of Ether Anesthesia," ^ as this action of oil of orange has been called, the following comment is made: "We are confronted here with a problem that has so far eluded solu- tion. The problem of noci and anoci associations finds instant solution, at least as far as its practical aspect is concerned. With a few drops of oil of orange (in alcoholic solution) we accomplish all that formerly demanded much preliminary psychic care, gas-oxygen inhalations, and injections of novocain, and quinin and urea hydrochlorid before and after anesthesia. Are pleasant odors narcotic to the olfactory nerve? Is that some explanation of their widespread and age-long use? Certain unpleasant odors are undoubtedly terrifying to animals, those of their enemies, for example. If pleasant odors are indeed sedative to the olfac- tory nerve, does that suffice to explain their extraordinary influence, at least when followed by ether, over the entire nervous system ? Is there ■ merely an association of ideas? The smell of ether is associated with the surgical knife in the minds of adults, and is terrifying to children from its irritating qualities. Perhaps the very familiarity and the harm- lessness associated with the odors of flowers and fruit are sufficient to suggest powerfully to the subject that what he is about to undergo can- not be dangerous, or even unfamiliar.'^ TTtilizing Carbon Dioxid. — The physiological importance of the car- bon dioxid content of the blood has only recently come to be fully recog- nized. Of still more recent origin is the demonstration of its relation to the administration of inhalation anesthetics. ^"A Mystery of Ether Anesthesia," Editorial, N. Y. Med. J., Sept. 14, 1912. GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 97 Extensive investigations by physiologists in America and Europe have established the fact that carbon dioxid is not merely a waste- product^ but performs a distinct role as a "harmone," or chemical-regu- lator of various functions. The carbon dioxid content of the blood, according to Henderson/ exercises regulative influences upon the heart- rate, upon the vascular tonus, upon the peristalsis of the alimentary canal, upon the mental condition, and upon a number of other functions of the body. From the data presented by him it appears that even a slight reduction in the carbon dioxid content of the arterial blood causes a marked quickening of the heart-rate. "Further reduction," he says, "induces an extreme tachycardia, complete cessation of peristalsis, failure of many reflexes, and coma. If an extreme reduction of the CO, content of the blood is effected very rapidly, the heart comes into a state bordering on tetanus. This cardiac tetanus practically abolishes the pumping action of the heart. Arterial pressure falls and death results. "If the reduction in the arterial CO2 is less extreme, but is main- tained for a considerable time (an hour or more, according to the extent of the reduction), so that the tension of COo in the venous blood and in the tissues is reduced, symptoms and conditions result which are sim- ilar, in many respects, to those occurring in mountain sickness and are apparently identical with those of surgical shock. Arterial pressure falls to a very low level, and, 'if the condition is continued, the circulation fails. The fall is not due merely to tachycardia, for the heart-rate in the later stages is not always extremely rapid, but is caused by a loss of tonus in the peripheral veins and capillaries, and by the consequent stag- nation of the blood in these vessels. The mental condition of the subject is comatose. The reflexes are greatly reduced in responsiveness. Vigor- ous stimulation of afferent nerves causes no rise of arterial pressure. The condition of the nervous system and the stage of excitement through which it develops are not due primarily to the fall -of arterial pressure. They precede the fall. Although the coma is, of course, intensified by a low pressure, it may occur to a considerable extent coincidently with the high pressure of the earlier stages. "The respiration, when the subject is left to breathe naturally, be- comes very shallow. It is liable to pass into apnea. This condition is the direct effect of the reduced CO, tension in the respiratory center." The reduction of carbon dioxid leading to the conditions described can be effected by various means detailed by Henderson, among which may be mentioned as having a practical bearing upon anesthesia: (1) artificial respiration; (2) the hyperpnea incident to the stage of excite- ment of incomplete anesthesia; (3) the hyperpnea produced by vigor- ^ Henderson, Yandell: "Acapnia and Shock," Am. J. Physiol., Feb. 1, 1908; Feb. 1. 1909; April' 1, 1909; Feb. 1, 1910; June 1, 1910; Nov. 1, 1910; Aug. 1, 1911. 98 ANESTHESIA ous and prolonged stimulation of the afferent nerves; (4) exposure of the abdominal viscera to the air so as to allow a free exhalation of carbon dioxid from the surface of these organs. Vq,riations in the oxygen con- tent of the blood, according to Henderson, play little part, if any, in the production of these conditions. The regulation of the carbon dioxid tension of the air in the pulmonary alveoli, and the extent to which carbon dioxid is eliminated from the blood in its passage through the lungs, appeared to him to be the most important factors in the preven- tion of shock. In experiments in which he had induced shock, Hender- son found that restoration of carbon dioxid to the tissues and blood (or rather the maintenance of a condition which permits the tissues rapidly to restore their CO2) proved effective in inducing rapid recovery. "Under all conditions, except during hyperpnea, in which condition the cardiac activity is increased sympathetically with the respiratory excite- ment, and, to a certain extent, even in this condition, the heart-rate can be kept down and the development of shock prevented." ^ It is important to note that in the absence of respiratory excitement the heart-rate is an index which varies inversely as the carbon dioxid content of the arterial blood. The investigations which led Henderson to make his extensive experiments and observations, and his own work, are briefly reviewed in the section on Shock (see p. 383). The experiments of Henderson and the observations of Mosso ^ led Levi,2 in 1910, to consider the practicability of utilizing mixtures of carbon dioxid with oxygen for the purpose of stimulating the bulbar centers in surgical cases in which the automatic activity of these centers is temporarily paralyzed in consequence of the effects of chloroform or ether, or operative trauma, or of a combination of these causes. He first experimented on animals. Failure of respiration was induced by means of the single or combined action of nitrites, chloroform, and morphin. The animals were then made to inhale a mixture of oxygen with carbon dioxid in percentages from 10 to 30. In every case he noted an almost immediate return of the breathing and the effects of the inhalation were ^ Henderson 's method for regulating the heart rate in his early experiments ' * depended upon the manipulation of the hand bellows with which artificial respiration was administered, and on the adjustment of the escape vent in the side of the cannula tied into the trachea. As the pulmonary ventilation was in- creased or diminished, the heart rate was correspondingly accelerated or retarded. ' ' 2 Mosso: Arch. exp. Path. u. Pharm., 1906, 54, 285. s Levi, Ettore: "The Clinical Use of Carbon Dioxid with Oxygen," J. Am. Med. Assn., March 16, 1912. Also : ' ' Nota preventia sulle applicazioni terapeutiche, nella pratica chirur- gica e medica di mischele li ossigeno e di anidriole carbonica, " Acad. med. fis., Frienze, March 16, 1910; "8tudi suU'azione fisiopatologica dell 'anidriole car- bonica, e sulle applicazioni terapeutiche, nella pratica chirurgica e medica, di mescele di ossigeno ed 'anidriole carbonica," Bev. Crit. di Clin. Med., 1910, Nos. 30 and 31. GENERAL PHYSIOLOGY OF INHALATION ANESTHESIA 99 •found to last for some time after the mixture had been discontinued. He then administered these gas mixtures to patients who were in a state of partial or complete coma as a consequence of trauma or extensive and prolonged operation. With mixtures of from 5 to 20 per cent of carbon dioxid in oxygen, the depth of breathing and the regularity of the rhythm were notably improved. His most satisfactory results were obtained with a mixture containing 15 per cent of carbon dioxid. In cases which exhibited Cheyne- Stokes respiration, normal breathing was restored, continuing so for some time after the inhalation of the gas mixture ceased. Marked improvement in circulation was also noted, the disappearance of cyanosis being one of the most striking features. In routine practice Levi employs the mixture of carbon dioxid and oxygen as soon as the slightest tendency to failure of respiratory or car- diac function appears. The almost invariable result, during nearly two years of experience with the method in hundreds of cases, has been a rapid return of normal heart action and breathing. The best results were noted where the condition of shock had not progressed too far, although striking beneficial results were obtained even in the latter cases. It is interesting to note that Levi's observations with this method seemed to him to afford an explanation, to some extent, of the good effects obtained with the method employed in connection with artificially reduced circulation (see Sequestration Method, p. 467). "It seems prob- able," he says, "that the remarkable rapidity with which patients sub- jected to narcosis under this condition recover consciousness, as observed by many authors, is due to the sudden return to the general circulation of a large amount of blood rich in carbon dioxid, when the lower limbs are unbandaged. Following up this suggestion, we have found that the use of a gas mixture containing from 10 per cent to 15 per cent of carbon dioxid after the completion of an operation is very effective in causing a prompt awakening of the patient. It seems also to tend to decrease the post-chloroformal vomiting. This is doubtless referable to the rapid elimination of chloroform from the blood and tissues under the influence of the increased respiration induced by the carbon dioxid." Levi does not give the technique by which he obtains the definite per- centages of carbon dioxid. Henderson has perfected an apparatus for definitely controlling the percentages of carbon dioxid. The requisite carbon dioxid percentage may be maintained by means of rebreathing as follows : When too much carbon dioxid is lost, as judged by the symptoms detailed (p. 97), the amount may be increased by allowing the subject to rebreathe for from three to six minutes, according to requirements, the anesthetic agent being discontinued meanwhile. When the breathing be- comes forced and other signs of distress appear, suggesting too much car- bon dioxid, rebreathing is discontinued and the administration of the an- esthetic is resumed. Four per cent has been found to be the limit of safety. CHAPTEE III THE USE OF EEBEEATHING IN THE ADMINISTRATION OF ANESTHETICS i W. D. Gatch, M.D. Ether: Effect of Ether Vapor on Eespiratory Passages; Compari- son of Toxic Effects Following Use of Open and Closed Methods; Ef- fect of Over-Concentration of Ether Vapor. JSTiTROUs OxiD Alone and Combined with Ether: Method of Administration; Basis of Technique; Practical Advice; Maintenance of Ether Balance; Elimination of Ether from the System; Effect of Mor- phin on Ether Elimination ; Clinical Eesults ; Long Operations ; Fatali- ties ; Cardiac Cases ; Hypercapnia ; Acapnia ; Ether and Acapnia ; Other Advantages of Eebreathing; Post- Anesthetic Nausea; Post- Anesthetic Abdominal Distention; Post- Anesthetic Lung Complications; Method Demands Experience. Chloroform and Ethyl Chlorid: Suggested Investigations; Dangers; Advantages. Eebreathing in the administration of ether and chloroform has been under discussion ever since the introduction of these agents as anes- thetics. With the introduction of etherization by the open method, rebreathing has fallen into disfavor, and many writers condemn it.^ When properly regulated, and when the oxygen supply is ample, rebreathing can be put to a valuable use. The evidence in favor of this is derived partly from a series of 3,500 nitrous oxid-oxygen and nitrous oxid-oxygen-ether anesthesias given by a closed method at Halsted's clinic, and partly from the recent and very important work of the ^ Taken from a paper read before the Section on Pathology and Physiology of the American Medical Association, at the Sixty-second Annual Session, Los Angeles, June, 1911. Eeprinted, with modifications, by courtesy of J. Am. Med. Assn. ^Cunningham and Anderson: "Methods of Administering Ether," J. Am. Med. Assn., Nov. 7, 1908, 1574. 100 REBREATHING IN ADMINISTRATION OF ANESTHETICS 101 physiologists, Henderson/ Hill,- Haldane,^ and others, on the carbon dioxid metabolism of the body. ETHER The subject can be approached most simply by considering the harm- ful results supposed to follow the administration of ether by the use of closed masks. Ether only will be, considered for the present, because most of the investigations bearing on the subject of rebreathing have dealt with this anesthetic. The ill effects in question may be grouped under two heads : (1) Injury to the lungs; (2) general toxic effects. Effect of Ether Vapor on Respiratory Passages. — Dreser,* Oifergeld,^ Poppert,^ and Holscher,'^ have studied very carefully the effects of ether vapor on the respiratory passages. Dreser regards any concentration of vapor which cannot be inhaled by the patient while in the conscious state without discomfort and coughing as harmful to the lungs. Applying this test he fixed on 6 to 7 per cent as the highest concentration which should be used. Offergeld, experimenting on animals, found that the lungs, after etherization by a closed method, showed much graver in- juries than after etherization by an open method. With the closed method he found extensive fatty degeneration and desquamation of the epithelium of the air-passages, also many minute hemorrhages into the alveoli; many of the animals died of bronchopneumonia. With the open method the pulmonary lesions were of a comparatively unimportant character, unless the administration was frequently repeated at short intervals. Poppert, whose experiments were similar to Offergeld's, con- cluded that ether vapor was more irritating to the lungs the greater its 'Henderson: "Acapnia and Shock" (a series of papers), Am. J. Physiol., 1908, n, 126; 1909, ^3, 345; 1909, ^4, 66; 1910, f5, 310; 1910, S6, 385; 1910, S6, 260; 1910, S7, 152. 2 Hill and Flack: "The Effect of Excess of Carbon Dioxide and of Want of Oxygen on the Eespiration and the Circulation," J. Physiol., June 30, 1908; "The Influence of Oxygen Inhalations on Muscular Work," J. Physiol., July 1, 1910. " Haldane and Poulton : * ' The Effects of Want of Oxygen on Eespiration, ' ' J. Physiol, 1908, 390. * Dreser : "A Contribution to the Study of Anesthesia by Ether, ' ' Johns Eoplcins Hosp. Bull., Jan., 1895. ^ Offergeld : ' ' Lungenkomplicationen nach Aethernarkosen, ' ' Arch. f. klin. Chir., 1907, 83, 505. * Poppert : ' * Experimen telle und klinische Beitrage zur Aethernarkose und zur Aether-Chloroform-Mischnarkose, " Tfeutsch. Z. Chir., 67, 505. ' Holscher : ' ' Experimentelle Untersuchungen iiber die Entstehung der Erkrankungen der Luf twege nach Aethernarkose, ' ' Arch. f. klin. Chir., 1898, 55, 175. 102 ANESTHESIA concentration. Holscher studied the distribution of secretion in the air- passages during ether narcosis. He found that there was only a very slight secretion from the epithelium situated below the level of the larynx. By putting coloring materials into the mouths of anesthetized animals he proved that mucus and saliva might be aspirated into the deepest air-passages. His conclusion was that "affections of the air- passages occurring after ether are, for the most part, due to the aspira- tion of infectious mouth contents." The experimental results dealing with the effects of ether vapor on the lungs may be summarized as follows: (1) The irritant action of the vapor varies according to its concen- tration. (2) Post-operative lung complications are frequently caused by the aspiration of mouth contents. (3) The greater severity of the pulmonary lesions found after experimental etherizations by the closed method can be satisfactorily accounted for by the great concentration of ether vapor in the closed masks and by the greater liability to aspirate mouth contents when these are used. Comparison of Toxic Effects Following the Use of Open and Closed Methods. — We now have to consider why the general toxic effects which follow ether anesthesia are more severe after the closed method than after the open method. Writers are almost unanimous in asserting that this is the case. The work of Ladd and Osgood ^ is very important in this connection. These authors studied the frequency of post-anesthetic vomiting in patients after etherization with the Blake cone, and in those etherized by the "gauze ether" method. Vomiting was much more fre- quent and severe among the former patients than among the latter. With the Blake cone cases they found acetone in the urine after opera- tion in 88 per cent of the cases, while with the "gauze ether" cases they found it in only 26 per cent. The technique and advantages of the open method are discussed by Miss Magaw,^ who reports 14,000 cases with most satisfactory results. In short, there is no doubt that this method of etherization is better than the rather crude closed methods that it has replaced. Its disadvantages and dangers will be referred to later. The causes commonly held responsible for the ill effects which follow the closed method are the following: (1) anoxemia; (2) overconcen- tration of ether vapor; (3) toxic organic substances in the expired air; and (4) excess of carbon dioxid in the expired air. There is reason to believe that the first and second of these possible causes are the real ones. From our present knowledge, the third is not ^Ladd and Osgood: "Gauze Ether," Ann. Surg., Sept., 1907. ' Magaw, Alice : "A Eeview of Over 14,000 Cases of Surgical Anesthesia, ' ' Surg., Gynec. and Obstet., 1906, 3, 795. REBREATHING IN ADMINISTRATION OF ANESTHETICS 103 important, since physiologists have demonstrated that there are no organic poisons in the expired air, or at least for practical purposes of anesthesia our clinical results indicate that such substances, even if they exist, need not be seriously considered.'^ The excess of carbon dioxid is harmless and can be utilized to good advantage. Effect of Overconcentration of Ether Vapor. — It is evident that anoxemia and overdosage of ether — evils almost unavoidable when this anesthetic is given in a tightly closed mask — must do harm. It is known that a deficiency of oxygen quickly causes the gravest injuries to the tissues. Dreser found that the gas within a closed etherizing mask would, at times, put out a burning candle. He also found that the ether vapor within the closed mask sometimes reached a concentration as high as 34 per cent, while 6 to 7 per cent is the greatest concentration which can be inhaled without irritation to the air-passages. With such an overdosage of ether as this, it is true that the excess of carbon dioxid within the closed mask is injurious, for it stimulates the respiration powerfully, and leads quickly to an overabsorption of ether by the blood. If the truth of what has just been stated be admitted, it follows that, if we can prevent anoxemia, overconcentration of vapor, and too great a depth of anesthesia, we can obviate most of the serious objections to the closed method of giving ether. NITROUS OXID, ALONE AND COMBINED WITH ETHER The principles laid down in the foregoing paragraphs have been used in developing a method of anesthesia, the technique and advantages of which will now be described. Nitrous oxid and, if necessary, ether are the anesthetics used. The apparatus employed ^ consists essentially of a mask connected by a piece of flexible tubing to a rubber bag. This forms a closed space into which the patient breathes. On the mask is a valve-box by means of which the patient can be made to breathe to and ^ Crowder, Thomas K. : "A Study of the Ventilation of Sleeping-Cars, ' ' Arch. Int. Med., Jan. 15, 1911, 85; Haldane and Smith: "The Physiologic Effects of Air Vitiated by Eespiration, " J. Path, and Bact., 1892 and 1893, 1, 168, 318; Erclents Fliigge: "Eeport of Experiments at the Institute of Hy- giene at Breslau," Z. f. Hyg., 1905, 363, 388, 405 and 433; Hill and Walker: "The Eelative Influence of the Heat and Chemical Impurity of Close Air," J. Physiol, Nov. 9, 1910. Rosenau and Amos (J. Med. Bes., 1911, 25, 35) claim to have found in the expired air minute quantities of organic matter. They expressly state, how- ever, that their work does not necessarily indicate that this material is poison- ous. Their results await confirmation. ^ The apparatus is described elsewhere in detail. It will be noted that the arrangement for giving ether has been changed so as to permit of a more ac- curate dosage. The method of administration is practically unchanged, except that Gatch now allows rebreathing for somewhat longer intervals. 104 ANESTHESIA fro into the bag, or to inspire from the bag and expire into the air, thus emptying the bag. The bag is attached to a small box, through which the current of gas must pass back and forth from the bag to mask. Into this box nitrous oxid and oxygen are admitted, and ether, drop by drop, from a receptacle above. The ether is vaporized in the box from a series Fig. 20. — Gatch Nitkous Oxid-Oxygen Apparatus. of drip-plates and any excess of liquid ether can be drained off at once by a stopcock. Method of Administration. — The mask is adjusted carefully to the patient's face and the bag filled with nitrous oxid containing a very small amount of oxygen. The patient is made to breathe this mixture in and out through valves, thus replacing all the air in his lungs with nitrous oxid and oxygen. The bag is next refilled with the same mix- ture of gases, which the patient is made to rebreathe for from five REBREATHING IN ADMINISTRATION OF ANESTHETICS 105 to eight minutes. At the end of this time he is allowed to empty the bag, breath by breath, into the air, after which it is refilled, and the same procedure is repeated. Oxygen is given, without any attempt to estimate its exact percentage to the nitrous oxid, in quantities just suffi- cient to prevent cyanosis. If desired, nitrous oxid can easily be given under positive pressure, by keeping the bag slightly overdistended. This is sometimes a useful procedure in managing difficult cases. Anes- thesia is usually established in less than two minutes. If the anesthesia is unsatisfactory with nitrous oxid alone, ether is added. This com- B. P. PULSE X o 200 190 180 170 150 160 140 130 120 110 100 160 160 140 130 120 110 100 80 80 70 60 60 66 '\ 1 \ 5: c 'n \ '■\ n ?! 45 40 35 30 26 20 16 10 5 s .'^ \ \f V -- r V. r \ J \ v/ N- J \ \ S, \ \/ A f V ■^ V V t/\ '■^ V Fig. 21. — Chart Showing Pulse and Respiration with Rebreathing. bined nitrous oxid-ether anesthesia has many points of practical and scientific interest. Ether is not given till the patient's respiration has been stimulated by the accumulation of carbon dioxid which results from the rebreath- ing. It is then added drop by drop. The heated gases quickly evaporate it from the drip plates, and it is rapidly absorbed by the blood because of the increased pulmonary ventilation. The most difficult svibjects can thus be deeply anesthetized. Basis of the Technique. — Eeference has already been made to Dreser's exj)eriments, in which he proved that from 6 to 7 per cent of ether vapor is the greatest concentration which can be inhaled by a patient in the conscious state without irritation and coughing. Precau- tions must be taken to keep the concentration of ether vapor in the mix- ture of gases below this level in order to eliminate the possibility of injuring the lungs. This is quite easily accomplished, as the following simple calculation will show. The gas-bag, moderately distended, holds about 10 liters of gas, the mask and tubing hold about 1 liter, and the entire respiratory system of the patient holds about 3 liters. When the 106 ANESTHESIA patient is rebreathing these all form one closed space, with a total capacity of about 15 liters. The problem therefore is simply to deter- mine how much ether must be added to 15 liters of gas in order to make the concentration of ether vapor 7 per cent. Abel has calculated the amount of ether to be 4.2 c.c. However, the conditions of the problem are so variable that the amount of ether required cannot be determined with absolute accuracy. The varying temperature in the apparatus, the loss of ether through leaks and by absorption in the lungs, are factors for which no accurate data can be 'furnished, as they are variable. But absolute accuracy is not necessary, because the constant loss of ether • PULsd RESP n r r n X O 180 170 160 160 140 130 120 110 100 140 130 120 110 100 90 80 70 60 50 46 40 36 30 25 20 IB 10 s ^ V ^ n v/ s, w V « rV ^ rt' ■to r/ >i \ ■,. V „ I It \ , -s V '^ V V * V a I 1 b 1 T . _ ^ ^ >»1 V •»< y V w ' ^ V • / V- V ^ _ _ Fig. 22. — Chart of the Pulse, Respiration and Blood-Pressure During Anesthesia OF Two Hours and Fifteen Minutes' Duration. Pulse: line with crosses. Res- piration: line with circles. Blood-pressure: line with heavy dots. The patient was a woman of 65 with carcinoma of the sigmoid. The operation was closure of a fecal fistula by double lateral anastomosis, repair of an old wound in the abdominal wall, and colostomy. Note the constant level of the pulse and the maintained rise of blood- pressure. The temperature rose from 98.6° to 99.9.° The recovery was excellent. gives us a wide margin of safety, so that ether can probably be added much faster than the calculation allows, without exceeding the danger limit. Practical Advice. — With the drops of ether falling at the rate of 130 to the minute, it has been found that it takes two and one-quarter min- utes to add the 4.2 c.c. Therefore, if we give ether at this rate and take precautions not to keep it dropping for more than two minutes at any one time, and to keep the bag constantly full of gas, we can be sure that the ether vapor will not reach a concentration greater than 7 per cent. The anesthetist can estimate the approximate strength of ether vapor by its odor as it escapes from the valve-box. Maintenance of Ether Balance. — It has been found unnecessary to give ether constantly during the administration. When enough has been given to produce satisfactory anesthesia, even in cases requiring a deep narcosis, the anesthesia can be maintained with nitrous oxid alone. This is to be explained by the fact that the rebreathing prevents the ether, once dissolved by the blood, from being thrown off as rapidly as REBREATHING IN ADMINISTRATION OF ANESTHETICS 107 it would otherwise be by the lungs, which are the organs by which it is practically all elim- inated.^ Suppose, for example, that a patient having a certain amount of ether dissolved in his blood is given some fresh nitrous oxid and oxygen to rebreathe. The ether will be thrown off from his lungs till the tension of its vapor in the gases being breathed will equal that in the blood. When this occurs no more ether will be eliminated until a new supply of gas is furnished. Elimination of Ether from the System. — Not only can we prevent the elimination of ether by rebreathing, but we can also hasten the elimination by a rapid ventilation of the lungs with fresh gas. During the process of rebreathing, carbon dioxid accumulates in the body and stimulates the respiratory center so that the breathing becomes deep and rapid — often fifty or sixty respirations to the minute. When a patient, anesthetized in the manner described, and breathing at such a rate, is given a fresh supply of gas and allowed to dis- charge each breath into the air, he apparently rapidly rids himself of the small dose of ether he has been given. Thus it is possible to anesthetize a patient so deeply that he will not stir during a Whitehead or other operation re- quiring deep narcosis, and yet have him con- scious before leaving the operating room. By careful administration we can, in most cases, keep the patient from knowing that he has been given any ether at all, so complete and rapid is its elimination. It is recommended that this method of re- moving a volatile anesthetic by rapid ventila- tion of the lungs he used at the close of every administration of chloroform or ether. The increased pulmonary ventilation can be easily H ...i'.... .-4 ,^ , 1 , < [ -4V i ■,:::[::,_ ■■ j J- r iV S; .i...l-i... 4 \ 1^1 «k ^ "^ \ . I -i S >: .-,... i \ ■''■ i k ■--:~--rl- -J .' VJ-S:^'" " c : ! ■ ■ Xa tl'. ■• / k _ r- -^ .r— /iC *t ! 1 f 5 ..^.J.„ - ... .._ t ' T S — L „ :_ Xl^ - -t n i 5 .1 „ ■"/T^ , jr ", T ■" :.: *": 'z ' i . T ■'■ " r^^ V .. ,14. "^ 1 ' -+-• L L. - J ,. I ! ....J I^: _j , t ... '. 4i ! i , 1 I [■ 4 1^ _.L.._rj '• 1 " -^ r L ._iTl. i ^ . \ \--'^t ;_ !_ ■« ^ ■ ^ ■**1 . _ .- i_ 1 ' 1 'i -, .. . .... : i'l I. ♦ * 1 i - r-4 -^M- ** 1 T-t-il- -}- T j ;■ i" . ' f.» • , -^ \ ..:1_, i T • V ; -|- --. *4 "1 ^"" ■ .' i • 4 - 1. ~H-j-X . ' J.. 1 IL" : i " ; ■ -■•«. ^... . i_ _.•.._ ' , ■' ■ - 1.: ! t 8 « 8 » ? « g ■ s S 1 1 s 1 r i ? 1 » s rf S > 1 £ 1 s 1 < § 1 V i« \' \' fl Fig. 23. — Chart Showing Value of Rebreathing During Operation. * Hewitt: "Anaesthetics and Their Administration," 3rd ed., 50; Cushny: "Pharmacology and Therapeutics," 4th ed., 166; Cushny: "The Exhalation of Drugs by the Lungs," J. Physiol., 40, 17; Nicloux: "Elimination de Tether contenu dans le sang apres I'anesthesie pendant la periode de retour, " Cornpt. rend. Soc. Mol, 1907, 1, 8. 108 ANESTHESIA brought about by making the patient breathe in and out, through valves, air or oxygen containing a small percentage of carbon dioxid. Effect of Morphin on Ether Elimination. — In this connection, it is interesting to consider the effect which morphin has on the elimination of ether or chloroform from the body. Morphin decreases markedly the rate of pulmonary ventilation.^ Large doses of this drug must therefore retard the elimination of the anesthetic and thus increase its toxic action. It is often possible to detect the odor of ether or chloroform on the patient's breath for several hours after operation. This slow excretion may be due, in part at least, to the morphin, a hypodermic of which is desirable before or after almost every anesthesia. Perhaps this effect of morphin can be alleviated by means of the method just described for the quick elimination of the anesthetic. During the stay of ether in the system its toxic action cannot be prevented. It has been found that the dose of ether, and its consequent ill effects, may be reduced to the minimum by employing a combination of this agent with nitrous oxid and morphin, the major part of the anesthesia, in this case being produced by the nitrous oxid and mor- phin. The effect of ether, when thus administered, is relatively much greater than when given alone, for, as is well known, narcotic drugs, given in combination, reinforce the action of one another.^ Thus the powerful joint effect of morphin and scopalamin has been explained. Clinical Results. — The form of anesthesia herein described has been in use in the surgical clinic of the Johns Hopkins Hospital for two years, over 2,500 patients having been anesthetized by this method. It is there the routine form of anesthesia for all operations, except those on the face, upper air-passages, or cranium. In these it has been found inconvenient on account of the difficulty of keeping the mask in place. Before the operation, the patient is given an enema and deprived of food for several hours, but is allowed to take small quantities of water. About thirty minutes before the anesthesia is begun a hypodermic of morphin and atropin is given, the dose for an adult being morphin 1/6 grain, atropin 1/100 grain. The anesthesia is started after the patient has been placed on the table and while the field of operation is being surrounded by sterile towels. It is established so quickly that the incision can usually be made in two minutes after the mask has been put on. Any depth of anesthesia which the condition of the patient and the nature of the operation may require can be easily obtained, because of the control of the patient's respiration which is given by the rebreath- ^Cushny: "Pharmacology and Therapeutics," 4th ed., 211. ^ Fiihner : ' ' Pharmakologische Untersuchungen iiber die Mischnarkose, ' ' Miinch. med. Woch., 1911, No. 4; Biirge: "Die Wirkung von Narkotikakom- binationen," Deutsch. med. Woch., 1910, No. 1, 20; No. 2, 62. REBREATHING IN ADMINISTRATION OF ANESTHETICS 109 ing. In abdominal operations, if the increased activity of the respiration is inconvenient, it can be prevented by giving a fresh supply of gas at frequent intervals. The bleeding during nitrous oxid-oxygen or nitrous oxid-ether anesthesia is about the same as during open ether anesthesia. The patient's temperature, provided he is kept dry and covered, will be found elevated from 0.5° to 2° after an hour's operation. Thus any special device for heating the gases is unnecessary, since the patient him- self attends to this.^ With light narcosis, under nitrous oxid and oxygen alone, the pulse may be rapid (from 140 to 160 to the minute), but this is of no significance, provided it is regular and of good quality, and there is no hemorrhage. The rapid heart-rate decreases when ether is given. Long Operations. — This form of anesthesia is especially well suited for long operations. In fact, the anesthesia does the patient so little harm that, within reasonable limits, the duration of the narcosis need not be considered. This is often advantageous to the surgeon, when deliberation and minute attention to detail are necessary. The following typical cases illustrate the method: Case 1. — The patient was a negro man, aged 27, in good physical condition. Operation: Excision of a sarcoma from the right popliteal space, and blood-vessel transplantation. Duration of anesthesia, five hours. The pulse-rate per minute varied from 72 to 100. The blood- pressure at the end of four hours of anesthesia was 130 mm. of mercury. The patient regained consciousness before leaving the table. He had no headache, nausea, or vomiting though he was given water at once. His urine after operation contained no albumin or acetone. He was allowed to rebreathe at two and one-half and three-minute intervals. The nar- cosis was deep and quiet. Ether was given with the gas for the first half hour. Case 2. — The patient was a white woman, aged 30, in rather poor condition. Operation: Eesection of the ascending and transverse colon. Duration of anesthesia, two hours and five minutes. No ether was used. The narcosis was light, the patient at times moving her limbs. Eecovery was immediate and unattended with headache or vomiting. Case 3. — The patient was a colored woman, aged 30, in good con- dition. Operation : Excision of the right breast, pectoral muscles and axillary glands for advanced cancer of the breast, Thiersch skin graft- ing of the raw surface of the breast. Duration of anesthesia, three hours and fifty-five minutes ; 21/0 ounces of ether, 130 gallons of gas and 30 of oxygen were used. The anesthesia was quiet and satisfac- tory, the recovery immediate and without headache, nausea, or vom- iting. ^On the subject of "Warmed Anesthetic Vapor," see Gwathmey, N. Y, J. Of Med., Feb., 1905. no ANESTHESIA Cautions. — A word of caution is, however, necessary. During any. administration, and especially during a long administration, the patient's breathing must be kept free and unobstructed, and his color good. If a patient has to work hard for every breath he soon wears himself out.. The color of the blood in the wound, the hue of the patient's face, and the character of his breathing, as shown by the movements of the rubber bag, are the best indicators of his condition. The surgeon himself can hardly fail to notice these. If the patient's breathing cannot be kept unobstructed, the use of the apparatus should be abandoned at once and some other method for the production of anesthesia employed. Fatalities. — Three fatalities, during or immediately after operation, in the series of 3,500 cases have been recorded. How much the an- esthesia was to blame for these may be judged from the following reports : Fatality 1. — The patient was a colored woman, aged 44, with ex- ophthalmic goiter of four years' standing. She had an irregular inter- mittent pulse, the rate of which had been between 120 and 140. Her heart was enlarged, and she had ascites and edema of the ankles. Dur- ing the last week of her life she had several severe attacks of dyspnea, associated with extreme rapidity and irregularity of the pulse. For these she was given a course of digitalis, which improved her condition so much that it was thought she could withstand a partial thyroidectomy. When the mask was placed over her face, she made a very slight struggle and took several shallow breaths. The operator then saw the superficial veins of her neck suddenly dilate. This apparently marked the time of death, and occurred within half a minute of the time the anesthetic was started. Fatality 2. — The patient was a man with aortic and mitral insuf- ficiency, on whom it was proposed to do' a perineal prostatectomy. He was given ether with the gas and oxygen. The anesthesia went very well till the patient was placed on the perineal table with his buttocks elevated; then he became cyanotic and died. An immediate autopsy revealed the presence of a large pericardial effusion, the presence of which had not been recognized before the operation. Fatality 3. — The patient was a girl of 16, with multiple infectious arthritis; general condition poor. Operation: Injection of both knees with oil and manipulation of knees, ankles, and elbows. Duration of anesthesia, fifteen minutes. The anesthesia was uneventful, except for a marked increase in pulse-rate while each joint was being manipu- lated. At no time was the breathing obstructed. At the close the pulse- rate went up very rapidly; the color became cyanotic and could not be cleared up with oxygen. The breathing became weaker and weaker, and finally ceased. An autopsy showed a very large thymus and hyper- REBREATHING IN ADMINISTRATION OF ANESTHETICS 111 trophy of all the lymphatic tissues. The pathologists gave status lyrn- pliaticus as the cause of death. The first and second of these patients had circulatory disease of such gravity that the anesthesia is not to be seriously blamed for the deaths. How the third fatality was brought about it is hard to under- stand. The toxicity of nitrous oxid is certainly too low to have caused it. Cardiac Cases. — ISTotwithstanding these fatalities, it is believed that this form of anesthesia, properly employed, is well suited for cardiac cases. Two cases of Cesarean section performed by J. W. Williams on women with serious valvular lesions will show the grounds for this belief. Both women were in about the seventh month of pregnancy, and in both delivery was necessary in order to save the life of the patient. One patient was in extremis and her death on the table was regarded by the operator as probable. Both women had such urgent dyspnea that the anesthetic had to be started with the patient sitting upright. The same method of administration was employed in each case. Each patient was given a hypodermic of morphin large enough to quiet her. In inducing anesthesia great care was exercised to avoid the least excitement or struggling on the part of the patient. Both were allowed to rebreathe oxygen till the respiration was stimulated before any nitrous oxid was given. Enough ether was used to give a quiet anesthesia. The operations were performed with the patients' bodies elevated at an angle of 20° to 30°. The pulse of both patients was much better during anesthesia than before, and the operator was able to proceed without undue haste. Both patients made an excellent recovery. Hypercapnia. — Clinical experience has certainly shown that an excess of carbon dioxid in the blood — a hypercapnia during anesthesia to the degree allowed — is harmless. Hill and Flack state that "the effects of carbon dioxid on the heart can always be quickly recovered from, even if the blood-pressure has sunk to zero." These authors found that car- bon dioxid up to a percentage of 35 in the air breathed stimulates the respiration, while above 35 it depresses it; also that percentages up to 22 produce a rise in blood pressure, while higher percentages cause a fall. Of course it is impracticable to determine exactly what per- centage of carbon dioxid a patient is breathing. The anesthetist must regulate the time of rebreathing so that the patient's respiration is moderately stimulated. The periods of rebreathing for 10 liters of gas range from three to five minutes, any leakage from the apparatus being meanwhile made up by the addition of fresh gas.^ ^ Alter rebreathing 10 liters of oxygen for three minutes, it was found to con- tain 8.9 per cent CO . Allowing for the decreased CO^ formation during anes- thesia, it is probable that the percentage breathed by the patient is seldom above this. 112 ANESTHESIA Acapnia. — Does a deficiency of carbon dioxid in the blood — acapnia — do serious harm? Henderson has been able to reduce animals to a state of extreme shock by overventilation of their lungs. He asserts that acapnia causes complex osmotic changes in the tissues, which result in a passage of water from the blood into the lymph and into the tissue- cells, and a dilatation of the finer veins. Interference with the normal filling of the right side of the heart by this process is the essential phe- nomenon in surgical shock. In extreme cases of acapnia the blood- stream is so scant and the respiration so feeble that the tissues do not receive the necessary amount of oxygen. An asphyxial acidosis results which does the body-cells irreparable injury. Whether Henderson's theory be accepted or not it must be admitted that the accumulation of carbon dioxid by the process of rebreathing is an efficient stimulus to the respiration and circulation. In fact, it is used as a purely thera- peutic measure in cases of morphin poisoning, in cases of so-called traumatic or toxemic shock, and wherever the respiration is feeble.^ Oxygen can be given much more effectually and cheaply by the use of rebreathing than in the ordinary way. Thus, with anesthetics of low toxicity and the use of rebreathing, a very ill patient may be benefited by an anesthetic. Ether and Acapnia. — On the other hand, when ether is given by the open method, we take a very efficient means of producing acapnia, because ether diminishes the formation of carbon dioxid by the tissues, and, by stimulating the respiration, hastens its elimination. Symptoms of a mild grade of acapnia under open ether anesthesia are com- mon. Thus a patient who has perhaps been difficult to anesthetize, or who has been lightly under ether for some time and is breathing at a rapid rate, will gradually stop breathing. After an interval of perhaps two or three minutes, his respiration will start again but will not be normal for a long time. This occurrence, though alarming, is seldom followed by harmful results. Hundreds of patients are etherized daily by the open method without developing symptoms of shock. What prevents a serious grade of acapnia in the great majority of cases ? Several factors are concerned.- (1) Many anesthesias are of too brief duration for acapnia to develop. (3) There is frequently more or less obstruction to the breathing during narcosis, and this prevents acapnia. ^Patients with feeble pulse and respiration — so-called shock cases — should be made to rebreathe air in oxygen till their respiration is normal, before breath- ing the anesthetic. ^Levi, Ettore: "Studies on the Patho-physiologic Action of CO^ and on the Therapeutic Applications in Surgery and Medicine of Mixture of O2 and CO2," Estr. d. rev. crit. di din. med., 1910, 11, 30, 31. REBREATHING IN ADMINISTRATION OF ANESTHETICS 113 (3) The slowing of the respiration which results from a prelim- inary hypodermic of morphin may protect from the same danger/ (4) The so-called "open" method is usually not "open" at all, for the mask is so covered with towels or gauze that the patient does con- siderable rebreathing. Other Advantages of Rebreathing. — Apart from the prevention of acapnia, rebreathing presents several other advantages over open ether anesthesia. The chief of these ar&: (1) Lessened post-anesthetic vomiting. (3) Decrease in number of cases of abdominal distention after operation. (3) Practical abolition of post-anesthetic lung complications.- Post-Anesthetic Nausea. — Vomiting after operation depends on many things besides the anesthetic. About 35 per cent of our patients vomit, but the vomiting is usually very slight. Of 200 patients only four had more than very transient vomiting. Of these cases one was a case of exophthalmic goiter, one a case of stone in the common bile-duct, one a case of spreading peritonitis from an appendix abscess, and one a case of intestinal reaction. The naasea alone seldom prevents a patient from taking water and nourishment at once after operation. Post-Anesthetic Abdominal Distention. — Very little experimental work has been done regarding the question of abdominal distention following ether anesthesia. Cannon and Murphy ^ observed a great delay in the emptying of the stomach contents into the duodenum, and a slowing of the passage of food along the intestines after etherization. Figure 24, which is a tracing obtained from D. E. Hooker,'' demonstrates ^Crile: "The Blood-pressure in Surgery," 281. ^ Homans : * ' Post-Anesthetic Pulmonary Complications, ' ' Bull. Johns Hop- Mns Eosp., April, 1909. ^ Cannon and Murphy : ' ' The Movements of the Stomach and Intestines in Some Surgical Conditions," Ann. Surg., 1906, 13, 513. * Thanks are due Dr. Hooker for permission to publish this tracing and for the following note: ' ' Dr. Gatch has asked to have added a note covering some unpublished experi- ments done in the physiologic laboratory of the Johns Hopkins University, which appear to have a direct bearing on his own work. ' ' Cross-sections of blood vessels or intestine, to which a recording lever was attached, were hung in a moist chamber. In the use of tissue from warm- blooded animals the temperature of the chamber was maintained constant at 35° C. Through the chamber were passed alternately streams of oxygen and carbon dioxid gas. By this method the tissue studied was exposed to practically pure atmospheres of the gases. The experimental conditions, therefore, did not fall within physiologic limits, so far as the percentage of gas is concerned. Work is now in progress to investigate the effect of different percentages of oxygen and carbon dioxid. Aside from the result of this future work, however, the interesting fact has been demonstrated that the musculature of the blood vessels responds in atmospheres of the gases studied in an exactly opposite manner 114 ANESTHESIA the paralyzing effect of a weak ether vapor on the pyloric ring of the frog. It also shows that carbon dioxid acts as a powerful stimulant to the muscle of the ring. Of course the conditions to which the bowel was subjected when this tracing was obtained were abnormal, yet the paraly- sis by ether -is exactly what any clinician would expect. It is well recog- nized that an excess of carbon dioxid in the blood promotes peristalsis, Fig. 24. — Tracing Obtained from the Pyloric Ring of a Frog Suspended in a Moist Chamber into Which Ether Vapor and Carbon Dioxid Could Be Passed. At c, carbon dioxid was passed over the muscle, causing a sharp contraction ; at ei very dilute ether vapor was turned on with the carbon dioxid, causing immediate relaxation; at 62 the ether was turned off. to the musculature of the intestines. Carbon dioxid causes a marked improve- ment in the tone of the intestines and a m^arked relaxation of tone in the veins and arteries. On tlie other hand, oxygen causes a relaxation of tone in the intestines and an improvement of tone in the veins and arteries. These results were obtained in the case of both warm-blooded and cold-blooded animals and demonstrated with graphic records. "If it be true that Henderson reasoned by analogy from the behavior of the smooth muscle in the intestine to that in the blood vessel (especially the veins) in developing the acapnia theory of surgical shock, it is obvious from these results that his reasoning was not entirely justifiable. "The correlation of the difference in action of these gases in physiologic economy tempts speculation. The body seeks to rid itself of any excess of car- bon dioxid. Jerusalem and Starling {J. Physiol., 1910, 40, 279) have shown that carbon dioxid (0.625 of an atmosphere) increases the efficiency of the isolated mammalian heart chiefly by improving its diastolic relaxation. Bayliss (J. Physiol., 1901, 26, 32) has shown that this gas relaxes vascular tone. It, has long been known that in the intestine the same gas increases peristalsis, and Mall {Johns HopMns Eosp. Bep., 1896, 1, 37) has suggested that rhythmic move- ments of the intestines may help to empty the venous plexuses in the walls and thus aid in driving the blood into the portal system. We have, therefore, a coordination of activity which greatly facilitates the circulation of blood and the consequent rapid elimination of the carbon dioxid. Oxygen in excess, on the contrary, would tend to bring about opposite effects with a resultant retarda- tion of the circulation. "In conclusion, it should be clear to the reader that this is a chemical regu- lation of the circulation entirely peripheral in its action. The action of the gases on the medullary centers is a wholly different question." REBREATHING IN ADMINISTRATION OF ANESTHETICS 115 aud Henderson^ has shown that the noriual ijitcstinal movements wliieh cease after a laparotomy can be restored by passing a stream of carbon dioxid over the exposed bowel. These experimental results are con- firmed by clinical experience. It will be recalled that we use the smallest possible amount of ether, and produce a hypercapnia by making a patient rebrcathe. In the 200 cases referred to above there was not a case of abdominal distention except after laparotomy, and among the laparoto- mies, seventy-five in number, it occurred in but three cases, these being the same patients who had considerable vomiting. Post-Anesthetic Lung Complications. — In 2,500 cases of nitrous oxid-oxygen or nitrous oxid-oxygen-ether anesthesia there was but one case of post-anesthetic pneumonia; this wa,s in a girl with general peritonitis, who recovered. This absence of pneumonia may have been partly accidental, since pneumonia after operation may be due to causes other than the anesthetic. The record is striking, however, and all the more so because patients wath pulmonary tuberculosis, bronchitis, and empyema were anesthetized without hesitation. It contrasts markedly with the record after open ether. Here in a series of 400 cases there was one death from ether pneumonia, and two deaths, one with autopsy, from acute pulmonary tuberculosis.^ The latter patients were both operated on for tuberculous glands of the neck. Both patients died rather late — in from two to three weeks — after operation, bvit they ran a high tem- perature from the first. It was the oj^inion of L. Y. Hammond, who had charge of the work on tuberculosis at the Johns Hopkins Hospital, that the etherization had lighted up small apical foci of disease un- detected before operation. Method Demands Experience. — The impression must not be gained that this form of anesthesia is free from danger. It is without danger so far as post-operative effects are concerned. During the administra- tion, however, there are dangers. These arise from causes which can generally be foreseen and which can always be j)revented by careful and skillful administration. The method should not be used except by those who have made a special study of its problems. CHLOROFORM AND ETHYL CHLORID Suggested Investigations. — The foregoing discussion of the use of rebreathing in the administration of ether and nitrous oxid will apply, in part at least, to the administration of all anesthetics given by inhala- tion. It would seem that rebreathing in the administration of chloro- ^ Henderson : "Shock after Laparotomy: Its Prevention, Production, and Eelief," Am. J. Physiol., 1909, 21, 60. ^ Walsh : ' * Chloroform Eather Than Ether Anesthesia in Tuberculosis, ' ' J. Am. Med, Assn., Aug. 28, 1909. 116 ANESTHESIA form and ethyl chlorid would be attended by the same advantages that exist in the giving of ether and nitrous oxid. The general principles which govern the administration of these agents by a closed method are : First: The problem of dosage, which must be taken into account because of the high toxicity of chloroform and ethyl chlorid. A definite measured quantity of the anesthetic should be added to each measured volume of the gas which serves as a vehicle for administering it. The narcosis should be begun with a very dilute anesthetic vapor. Second: AVhen once anesthesia is established, it should be main- tained in the same way as with an ether anesthesia, namely, by pre- venting the elimination of the drug from the patient's blood by making him rebreathe oxygen or air. The elimination of the anesthetic at the close of the narcosis could be hastened by overventilation of the patient's lungs. Dangers. — The chief dangers of this method are: (1) Anoxemia due to a failure to give sufficient oxygen or to an obstructed airway. (2) Impediments to the respiration, which, in a long anesthesia, may exhaust the patient. (3) With cardiac cases, .excitement during the period of induction. Advantages. — The chief advantages of this method are : (1) The rapidity and pleasantness with which anesthesia is estab- lished. (2) The ease with which any depth of anesthesia can be secured. (3) The prevention, to a very large extent, of post-anesthetic vom- iting, pulmonary complications, and abdominal distention. CHAPTER TV NITEOUS OXID HiSTOEY : Early Use in Dentistry ; Nitrons Oxid Administered with Oxygen; Physical Properties; Chemical Properties; Impurities of Nitrous Oxid; Standard of Purity. Special Physiology: The Hyperoxygenation Theory; The De- oxygenation or Asphyxiation Theory ; The Theory of the Specific Action of Nitrous Oxid upon the Brain Cells; Effects upon the Respiratory System; Effects upon the Circulatory System; Effects upon the Nervous System ; Effects upon the Muscular System ; Effects upon the Glandular System and Other Structures; Causes of Death; Stages of Anesthesia; Elimination ; After-effects. Comparison with Other Agents. Indications and Contraindications. Administration : Heating the Gas ; Essential Features of Any Satisfactory Apparatus; Apparatus for Administering Nitrous Oxid Alone or With Air; Dangers of Administration of Nitrous Oxid Alone; Recognition of Asphyxial Symptoms; Administration of Nitrous Oxid Alone; Administration to Asphyxiation With and Without Valves; Use of Expiratory Valve Alone; Administration Without Valves; Precau- tions When Administered Alone; Administration of Nitrous Oxid With Air in Unknown Quantities ; Administration of Nitrous Oxid With Defi- nite Amounts of Air; Nitrous Oxid as a Sequence to Ether; Nitrous Oxid With Air; Technique of Ether-Nitrous Oxid (Air) Sequences; Technique With A.C.E. ; Advantages of Ether (or Chloroform-Ether) - Nitrous Oxid Sequence; The Advantages of Administration of Nitrous Oxid With Oxygen; Superiority of Oxygen Over Air; The Administra- tion of Nitrous Oxid With Indefinite Quantities of Oxygen; Catch's Method of Administration; Davis' Method; Methods of Administration With Definite (Quantities of Nitrous Oxid and Oxygen; Gwathmey's Method; Teter's Method; Technique to be Followed in Administering Nitrous Oxid and Oxygen With the Teter Apparatus and the Teter Nasal Inhaler; Nitrous Oxid Oxygen Endopharyngeally ; Boothby, and Cotton Apparatus; The Gwathmey-Woolsey Nitrous Oxid-Oxygen Apparatus. 117 118 ANESTHESIA HISTORY In 1772, Priestley ^ discovered nitrous oxid, called by him "dephlo- gisticated nitrous air," by reducing nitrogen dioxid (NOo), "gaseous oxide of azot/' with moist iron filings. In 1793, Deimann and others prepared the gas by heating ammonium nitrate (]SrH4N03), essentially the commercial process for its manufacture to-day. In 1798, the "Pneumatic Institute" was founded for the purpose of investigating the "medical powers of factitious airs or gases" and was set up at Clifton by Dr. Beddoes. The immediate idea to be followed out was the treatment of phthisis and other lung troubles by inhalation of various gases. Humphrey Davy was assigned the office of superin- tending the experiments. One of the first outcomes of his researches, the result of his experimentation with nitrous oxid upon animals, is given in the f olloAving historical and often qiioted sentence :^ "As nitrous oxid in its extensive operation appears capable of destroying physical pain, it may probably be used to advantage during surgical operations in which no great effusion of blood takes place." Then Davy actually inhaled the gas and recorded his own sensations and the behavior of others after they had inhaled it. Early Use in Dentistry. — In Decembisr, 1844, Colton delivered a lec- ture on nitrous oxid and other gases in Hartford, Connecticut. Horace Wells, a dentist of that place, was present. He noticed that a person under the influence of the gas was capable of sustaining a severe injury without apparently feeling any pain. This fact so impressed him that he requested Colton to administer the gas to him, and, while under its influence, had a tooth extracted without feeling the least pain. Upon regaining consciousness, he exclaimed, "A new era in tooth-pulling." From that time on he administered the gas to his patients with more or less success.^ With the death of Wells, which occurred in 1848, and the introduction of ether, nitrous oxid was not thought of again as an anesthetic until Colton revived its use in 1863. Kymer in England and Hermann in Germany also imdertook (18G4-1866) some experiments with nitrous oxid. ^"Experiments and Observations on Different Kinds of Air," 1, 3; "Mem- oirs of Joseph Priestley to the Year 1795," 1803, 1. ^Davy: "Eesearches, Chemical and Philosophical, Chiefly Concerning Nitrous Oxide," London, 1800. ^IJpon attempting to make a public exhibition at the Massachusetts General Hospital the inhaler was removed, possibly too soon, and the patient gave a piercing cry. Wells was immediately looked upon as an imposter. He, a modest, retiring man, felt the imputation deeply, and, while continuing to ad- minister the gas in private, never summoned sufficient courage to attempt an- other public exhibition. Later he gave up the practice of dentistry, became more or less unsettled in his mind, and died by his own hand. NITROUS OXID 119 In 1867^ Colton was able to give a record of twenty thousand suc- cessful cases; and in 1868 an auspicious demonstration took place at the Dental Hospital in London, mainly through the financial assistance and patronage of the well-known American dentist, Evans, of Paris. At this period it was considered safe for short operations. Some sur- geons, however, declaimed against nitrous oxid as unsatis- factory and dangerous. Never- theless, a Joint Committee of the Odontological Society and of the Dental Hospital reported so favorably upon the value of the gas that it has since occu- pied the foremost place as an anesthetic in modern dentistry Nitrous Oxid Administered with Oxygen. — In 1868, An- drews published accounts of a number of cases in which he had obtained a non-asphyxial form of anesthesia by using oxy- gen with nitrous oxid. It is now well established that an efficient anesthesia can be maintained by administering definite percentages of air with the gas. Also, by combining nitrous oxid with oxygen we may obtain a deeper, more satisfactory and safer anesthesia. Further- more, by warming a mixture of the gas and oxygen, and by the addition of small amounts of ether and chloroform, a satisfactory form of anes- thesia can be maintained for over 80 per cent of all surgical cases. Brown, of Cleveland, Ohio, was the first to use a warmed mixture of nitrous oxid and oxygen.^ Clover and Coleman first attempted the con- tinuous administration of nitrous oxid through the nose. Patterson, in 1899, improved upon this, and Kilpatrick,^ in 1902, still further im- proved this method by placing a regulation expiratory valve upon the nose- piece. Teter improved the technique of nasal anesthesia by using oxygen and warm nitrous oxid with a perfected nosepiece. Karl Connell, of Eoosevelt Hospital, has only recently improved the technique of admin- istering nitrous oxid and oxygen by using nasal catheters and a pharyn- ^ The first recorded experimentation with these gases at different tempera- tures on lower animals was by Gwathmey in 1906. "Medical Press, July 18, 1902. Fig. 25. — Gardner Q. Colton. 120 ANESTHESIA geal breathing tube to maintain a clear airway and also by rebreathing to decrease the amount of gases used. Physical Properties. — Nitrous oxid, "laughing gas," nitrogen prot- oxid, nitrogen monoxid, ISTgO, is a colorless gas at ordinary tempera- tures; it possesses a specific gravity of 1.527. One liter of the gas weighs 1.97 gm. ; 100 cubic inches weigh 47.29 gm. Under a pressure of 50 atmospheres at + 7° C. (+44.6° F.) or 30 atmospheres at 0° C, it is converted into a colorless mobile liquid having a density of 0.937 (at 0° C.) ; ^ the liquid has the lowest refractive index of all liquids. The ease with which it may be liquefied is taken advantage of and liquid nitrous oxid is supplied on the market in steel cylinders of various capacities. A convenient size for short operations, or for preliminary administration to produce unconsciousness before the use of ether or chloroform, is a small tube weighing about 39 ounces gross, which holds 6 ounces of the gas. For hospital work vanadium-steel cylinders holding 200 to 250 gallons of the gas are serviceable.^ Fifteen ounces of the liquid on evaporation yield about fifty gallons of the gas. The cylinders usually, and should always, have a statement upon an attached label indicating the weight of liquid within. By remembering that an ounce of the liquid yields about three and one-third gallons of the gas, at ordinary room temperature and pressure, the operator can readily know the amount of gas at his disposal. By weighing before and after use each time, and entering the difference upon the label, the anesthetist always knows what his supply is. This information is of vital impor- tance in some cases. Nitrous oxid, like other gases, expands when heated. The gas and liquid within the cylinder are under a theoretical pressure of at least 750 pounds per square inch even below room temperature. Often the pressure is over 1,000 pounds per square inch. If the cylinders are sub- jected to undue heat, the pressure may become so great as to burst the cylinder, producing serious consequences; therefore, any unnecessary heating of the cylinder should be avoided. Such accidental explosions have occurred. The boiling point of nitrous oxid at 760 mm. pressure is — 90° C; the freezing point is — 102° C. If the liquid is allowed to escape under atmospheric pressure through a small orifice, part of it is converted into a compact snow,^ which has a temperature of — 100° C. This snow, along with some ice produced from the moisture of the air by the low ^Faraday, 1823. ^ According to the best modern practice, vanadium-steel cylinders are the safest, for, even if they burst, they are not shattered, but simply split along the seam. ' Wills : "A Modification of Thilorier 's Method for Preparing Solid Carbon Dioxide," J. Chem. Soc, 12, ii, 21. NITROUS OXID 121 temperature, may sometimes choke the outlet and interfere with the regular flow of the gas. This difficulty will never be encountered when small amounts of the gas are used, if the simple precaution be taken to keep the outlet well above the level of the liquid within — in short, if the gas is drawn off with the cylinder in a vertical position, outlet upward.^ When, however, the gas is to be used in prolonged cases it is desirable to heat the outlet. Liquid nitrous oxid may be preserved with perfect safety for an indefinite time in steel cylinders provided with good valves. Some administrators " have noted differences between nitrous oxid which had and had not been liquefied. These differences undoubtedly were due to the admission of undetermined and variable amounts of air in prepara- tion for or during administration, or to temperature conditions brought about by administering the gas from the liquid without the warming referred to above. ^ Nitrous oxid is soluble in water, volume for volume, at 0° C. ; the solubility diminishes greatly on elevation of the temperature of the water. The solution seems to be mainly physical, as we have no evidence of chemical union between the nitrous oxid and water as in the case of carbon dioxid and water, beyond the formation of an unstable hydroxid, N2O6H2O, at 0° C. The gas may be collected over warm water. It is quite soluble in absolute alcohol at zero. Chemical Properties. — Nitrous oxid is quite stable, not being decom- posed into its elementary constituents by heat, unless the temperature is very high. It supports combustion, if the combustion has been actively started; that is, a strongly burning taper is not extinguished when plunged into the gas, but continues to burn, utilizing the oxygen and liberating the nitrogen. Nitrous oxid has a pleasant odor and a slightly sweet taste. It may be respired without discomfort, with suitable ap- paratus. When pure it exhibits no irritant properties. Impurities of Nitrous Oxid. — The manufacture of nitrous oxid de- pends upon heating ammonium nitrate, NH,N03==N20+2H20; or some combination of salts which produces ammonium nitrate, as, for example, KNOa + NH.Cl; SNaNOg + (NHJ3PO,; or 2NaN03 + ^ In connection with the devices for using cylinders in the horizontal position, see Sheppard: Lancet, 1891, 424; Hewitt, "Anaesthetics," 3rd ed., 268. ^Eoberts: Brit. J. Dent. Sci., Dee. 15, 1884. "Smith and Leman: J. Am. Chem. Soc, 1911, 33, 1116, give analytical results indicating a difference in the gas when drawn from cylinders with the outlet upward or reversed. They state that there is less nitrous oxid and more air (than that originally in the cylinder) in the gas when first drawn from the upright cylinders. Cylinders should have all the air removed before filling. If this has not been the case and the cylinder is thoroughly shaken just before the use, the gas is of uniform composition, as has been, shown by Baskerville. 122 ANESTHESIA (^114)2804.^ The impurities liable to be present depend upon the materials used, proportions present, heat treatment, and conditions of the pumps and containers. ^ Compressed nitrous oxid obtained in the American market from different manufacturers gave on analysis the following values: ANALYSIS* Sample No. N2O H2O CO2 NH3 O2 N2,etc. bydiff. N20by explo- sion N2O by Cu + CO2+H2 NsOby Cu + H2 1 99.7 0.13 0.006 Present 0.16 97.5 99.4 99.7 2 96.6 0.15 0.001 Present 3.25 95.0 96.2 96.6 3 99.5 0.15 Present 0.35 97.3 99.3 99.5 4 95.9 0.16 Present Present 3.94 94.1 95.6 95.9 * Baskerville and Stevenson, loc cit. Tlie last column gives the figures con- tained by the new method devised by them. Smith and Leman analyzed four cylinders of liquid nitrous oxid from different manufacturers, with the results shown on page 123.^ Standard of Purity. — Nitrous oxid which is to be used for anesthetic purposes should contain at least 95 per cent of NgO and no solids, * One of the authors (C. B.), in conjunction with Stevenson, has made an investigation of this subject and devised methods of analysis, for the details of which see J. Ind. and Eng. Chem., Aug., 1911. Erdman and Stolzenberg, Berlin, 43, 1708, Willard, Compt. rend. (1894) 118, 646, found that a hydrate of nitrous oxid (N2O.6H2O) may be obtained by keeping at 0°, in a sealed tube, a mixture of liquid nitrous oxid and water. Ice does not appear to react with nitrous oxid. Willard {ibid., 118, 1096) found that nitrous oxid may be freed from air and nitrogen, the commonest contaminants, according to him, by the preparation of this hydrate, which, although scarcely decomposed below 0° under ordinary pressure, furnishes about 200 times its volume of gas when warmed above this temperature. He devised an apparatus for the purification of nitrous oxid by this means. [Ann. Chim. Phys. (7), 11, 289.] ^ Commercial nitrous oxid is apt to contain these impurities : CI2, No, NO2, HNO3, NH3, HCl, CO2, O2, Nj, rare gases of the air, and organic matter (from lubricants). Of these the first six only produce any irritation of the respiratory mucous membrane, and they are usually removed in its manufacture, if present, by washing the gas in turn with solutions of sodium hydroxid, fer- rous sulphate, and sulphuric acid. Further purification may be accomplished by the formation of a hydrate below 0° C, by fractional condensation and subsequent fractional distillation. V. Am. Med. Assn., 57, No. 7. NITROUS OXID 123 Percentage of Nitrous oxid . Oxygen Nitrogen . . . . Carbon dioxid No. 1 95.4 0.0 4.6 0.0 No. 2 No. 3 93.4 95.8 1.4 1.1 5.2 3.1 0.0 0.0 No. 4 96.1 0.1 3.5 0.3 liquids, combustible organic matter, chlorin, or other oxids of nitrogen. ^ The last two impurities may be tested for by slowly passing 10 liters through silver nitrate and ferrous sulphate solutions. No precipitate should be produced in the former, and no brown or black coloration in the latter. SPECIAL PHYSIOLOGY The evolution of knowledge concerning the physiological action of nitrous oxid administered by inhalation is striking and the changes of opinion are radical. The conceptions of the physiological action of this agent have, in a large measure, been controlled by the clinical methods of administration employed at various times. Three distinct steps in this process of elimination and np-building, based upon experimental and clinical data, may be traced. The Hyperoxygenation Theory. — Sir Humphrey Davy believed that nitrous oxid was decomposed into its constituents, nitrogen and oxy- gen, during its passage through the circulation. It was thought that this produced superoxygenation of the blood, and that this overproduc- tion of oxygen led to the formation of unusual amounts of carbon dioxid, which, in turn, produced a form of "internal asphyxia." Oliver and Garrett ^ examined the gases of the blood of a dog while under nitrous oxid, with the results shown on page 124. From these figures it will be seen that there is undoubtedly a large increase in nitrogen in the blood after nitrous oxid inhalation. There seems, however, to be no conclusive evidence that nitrous oxid splits up in the organism, the gas being too stable to be decomposed at the tem- perature of the blood. The increase in nitrogen, as shown by the fore- ^ Lack of knowledge of the content of real ISTjO may seriously interfere with the satisfactory use of this, the safest, anesthetic, especially when it is admin- istered by the proper method, namely, mixed with oxygen. If the preparation contains more than 95 per cent NjO, the variation in the proportion of the two gases will depend then, in fact, upon the amount of oxygen actually mixed, and the percentage is not seriously altered. "^Lancet, 1893, 683. (The analytical methods and technique employed in these determinations are not known.) 124 ANESTHESIA Normal Before After Dog Inhalation Inhalation qo, 34.3 15.66 0, 22.0 3.49 N, 1.8 11.23 N2O 22.49 going figures^, remains unexplained. Frankland ^ analyzed the expira- tory products of several administrations and failed to find any distinct evidence of decomposition. The theory, therefore, that the brain cells are overpowered, so to speak, by an excess of oxygen, with the resulting phenomenon of anesthesia, was abandoned as being untenable. The Deoxygenation or Asphyxiation Theory. — When it became fairly well established that nitrous oxid is too stable a gas to be decomposed upon its entrance into the circulation, as formerly supposed, opinion swayed in the opposite direction, and the theory proposed was that, the hemoglobin of the blood having a greater affinity for nitrous oxid than for oxygen the oxygen becomes displaced from the lungs and other tis- sues by the nitrous oxid, the brain cells and nervous centers being thus starved, so far as oxygen is concerned, are smothered, as it were, by nitrous oxid. To this condition the term asphyxiation is applied, and unconsciousness, or anesthesia, is the inevitable result. This mechanical displacement of oxygen by nitrous oxid, leading to "tissue asphyxia,'^ has been characterized as a more dangerous view, from a practical stand- point, than the hyperoxygenation theory. Hermann ^ concluded that nitrous oxid was simply absorbed by the blood plasma, and that its action was only that of asphyxiation, the con- ditions being accounted for by the exclusion of the oxygen normally breathed. He found that one hundred volumes of blood at body tem- perature would absorb sixty volumes of nitrous oxid. This ratio was later fixed by Bert as one hundred to forty-five. This theory of so-called deoxygenation has been supported by Jolyet, Blance, Duret, Johnson, Eeid, Amory, Wood, Cerna, and many others, and lately by Crile. This theory held sway, as did the short-lived preceding hyperoxy- genation theory, during the period when nitrous oxid was used almost exclusively for dental and very short surgical operations. During this time nitrous oxid was rarely inhaled pure. It was not only difficult to obtain a pure gas, but, when obtained, it was administered in such a way that it was variably diluted with air, the effects produced being, as a ^ St. Bartholomew's Hospital Becord V. "Brit. Med. J., 1868, 378. NITROUS OXID 125 rule, those of intoxication rather than anesthesia. Inasmuch as air exclusion, or oxygen exclusion, was considered the prime factor, the apparatus devised during that period aimed at this object. The appara- tus devised by Colton was fitted with inspiratory and expiratory valves for the purpose of accomplishing the rigid exclusion of air. The Theory of the Specific Action of Nitrous Oxid upon the Brain Cells. — Despite the fact that air-exclusion was aimed at, it was soon found that the alternate inhalation of nitrous oxid and air served to maintain a more or less complete anesthesia for protracted surgical operations. The asphyxiation theory was generally accepted until An- drews,^ in 1868 (see History, p. 34), showed that anesthesia could be maintained over a longer or shorter time at will, by mixing oxygen with nitrous oxid. This, quite naturally, upset the deoxygenation theory, and led to the conclusion that the nitrous oxid must exercise some specific action upon the train cells.. The observations of Bert^ and the early experiments of Buxton ^ verified the hypothesis that nitrous oxid produced narcosis by virtue of other than asphyxiating qualities. This theory has held its own up to the present time, the variation of opinion bearing reference to what constitutes the specific action of nitrous oxid upon the nervous centers. Kemp,* following a series of experiments begun in 1890, for the pur- pose of determining the validity or invalidity of the deoxygenation theory of nitrous oxid anesthesia, as the result of fourteen experiments, took a position intermediate between those who hold that the action of nitrous oxid and of nitrogen is the same, and those who hold that nitrous oxid is simply an indifferent gas, acting like nitrogen. He found that the difference in the action of the two gases, when given pure, was so masked by the rapid onset of asphyxia that any wide-reaching generalizations were unsatisfactory. Two points, however, he considered worthy of especial notice: (1) That anesthesia was induced more quickly with nitrous oxid than with nitrogen; (2) that the muscular movements which always supervene upon deprivation of oxygen were milder with nitrous oxid than with nitrogen. A second set of experiments was conducted by Kemp, in which enough oxygen was given to sustain the life of the animal while the action of nitrous oxid and of nitrogen was being studied. These experiments lead up to the present-day methods of administer- ing nitrous oxid, and to the modification of the physiological action of ^Andrews: J. Brit. Bent. Sci., 1869, 22. 2 Bert : ' ' Pression iDaroraetrique. ' ' * Buxton, Dudley W. : (1) "On the Physiological Action of Nitrous Oxide," Trans, Odontological Soc. of Great Brit., 1886, n. s., 18, 133; (2) IMd., 1887, n. s., 19, 90. *Kemp, G. T. : "Nitrous Oxide Anesthesia," Brit Med. J., Nor. 20, 1897, 1480. 126 ANESTHESIA this and other iuhalation anesthetic agents by oxygen, as detailed in the chapter on General Physiology, p. 30. In the following discussion of the action of nitrous oxid upon the organism it is to be borne in mind that the gas, given alone, is under consideration. It is especially to be remembered, however, that the administration of nitrous oxid alone belongs to the past and not to the present period of the science of the administration of anesthetics. Brunn,^ who discusses the mode of action of nitrous oxid, recalls the demonstration by Bert of a specific narcotic efficiency on the part of nitrous oxid. Bert successfully avoided the onset of asphyxia by means of the inhalation of the nitrous oxid-oxygen mixture under pressure, proving at the same time that the narcosis could be arbitrarily length- ened. In this way he demonstrated the accuracy of his theoretical reflec- tion, that it is the over-low partial pressure of the nitrous oxid — in the nitrous oxid and oxygen mixture as inhaled under ordinary atmospheric pressure — which prevents a sufficient absorption of nitrous oxid in the blood for the onset of narcosis. This deficit was successfully remedied by Bert through raising this partial pressure to the level of the atmos- pheric pressure. Brunn emphasizes the fact that in order to understand the mode of action of nitrous oxid it is necessary to keep carefully apart the experi- ments with the inhalation of pure nitrous oxid — which always involves two factors, namely, the nitrous oxid action and the asphyxiation — and the experiments with the inhalation of nitrous oxid under a simul- taneous supply of a sufficient quantity of oxygen. Brunn refers to a series of fundamental experiments which were made by Goldstein,^ who showed the narcotic effect of nitrous oxid on frogs. In comparative experiments, a frog ceased to react after five and a half minutes to strong external stimuli, in a nitrous oxid atmosphere, whereas the same frog had not yet lost its power of reaction after an hour and a quarter in a pure hydrogen atmosphere. However, the nitrous oxid narcosis was made to disappear again by the admixture of a small quantity of air. For the explanation of this phenomenon, Goldstein regarded the assumption of diminished partial pressure as insufficient, and he believed, in contradistinction to Bert's views, that a rapid and complete narcosis was produced and maintained only when the effect of the nitrous oxid was combined witli that of a deficiency in oxygen. This statement certainly holds good for "ordinary" nitrous oxid anesthesia, but he admitted himself that in a greater density of the nitrous oxid this was alone sufficient for the production of a complete narcosis. ^ Brunn, M. v. : " Die Stickoxydulnarkose, " " Die allgemein Narkose, ' ' 1913, 325. -Brunn; Die allgemein Narkose, " 1913, 325 et seq. NITROUS OXID 127 The study of the respiration of warm-blooded animals, under the effect of nitrous oxid, first led Goldstein to recognize the fact that in rabbits the respiration gradually becomes slower and more superficial, in an inclosed space with air as well as in a mixture of nitrous oxid and oxygej^,, until the respiration finally ceases, at 3-4 per cent oxygen contents of the gas mixture, without preceding signs of dyspnea. In sudden asphyxiation Goldstein distinguished three stages. The first is characterized by inspiratory efforts, to which are added, in the second stage, violent expiratory muscular efforts, corhbined with clonic convul- sions; in the third stage there are infrequent inspiratory movements, the expiratory muscles remaining entirely inactive. Comparative experi- ments, with inhalation of nitrogen on the one hand and nitrous oxid on the other, yielded considerable differences. In the case of nitrous oxid, narcotic effects are almost instantaneously manifested, so that the dyspneic efforts do not reach nearly the same degree as in breathing nitrogen. The clonic convulsions are altogether absent. The second stage of the asphyxiation is more rapidly terminated. The most impor- tant difference, however, as compared to ordinary asphyxiation, accord- ing to Goldstein, is the appearance of loss of reflexes only just before the respiratory paralysis, namely, in the second half of the third stage of asphyxiation in ordinary asphyxiation; whereas, in nitrous oxid inhalation, the loss of reflexes is already present in the second stage, namely, long before the respiratory center is endangered. In Goldstein's experience the inhalation of a mixture of 73 per cent nitrous oxid and 27 per cent oxygen, in dogs, was followed by a diminu- tion in the number of respirations, while the depth was increased. The anesthesia, according to Goldstein, appears the more rapidly, and with a proportionately less degree of asphyxia, the higher the organization of the brain — namely, earlier in man than in the laboratory animals. Effects upon the Respiratory System. — Experimental observations have established the fact that nitrous oxid, given pure, or alone, rapidly induces asphyxia by gradual paralysis of the respiratory center in con- sequence of the prolonged action of the increasingly deoxygenated, or venous, blood. The respirations, which at first become more rapid and deep, become convulsive as the deoxygenation process is continued, then slow and shallow, finally ceasing altogether. When the asphyxial ele- ment is absent, the convulsive character of the respirations is not noted. Numerous experiments with animals have established the fact that when death is caused by pure nitrous oxid the usual post mortem signs of asphyxia are present. It has been emphasized by Hewitt ^ that the character of the pulse is greatly dependent upon the fullness and efii- ciency of the respiration. Whatever differences there may be between the phenomena produced by nitrous oxid, by nitrogen, and by mechan- ^ Hewitt: "Anaesthetics," 1912, 90. 128 ANESTHESIA ical closure of the trachea, one and all, according to Hewitt, lead to fatal asphyxia. Because of the lessened amount of tissue change which takes place in nitrous oxid anesthesia, the quantity of carbon dioxid given off by the lungs is. decreased. The significance of this, with reference to the practical question of shock, is considered in the Chapter on Treatment Before, During, and After Anesthesia. JSTitrous oxid is not injurious to the lungs, being a non-irritating gas. The bronchial irritation of which some have complained is par- tially eliminated by warming the agent (see Chapter on General Phys- iology, p. 64). It is still further eliminated by passing the gases through water, as described on page 323. For men, Goldstein ^ emphasizes the point that anesthesia sufficing for the performance of brief operations is already present prior to the extinction of the reflexes, at a time when the respiration is regular, deep, and of almost normal frequency. The pulse at this time is also approximately normal and of increased volume. Effects upon the Circulatory System. — There is a divergence of opin- ion concerning the actual role played by nitrous oxid in the Mood. According to Buxton's ^ view, nitrous oxid, when administered pure, enters the blood by diffusing through the thin walls of the air-cells in the lungs. A small quantity is dissolved in the blood, but the bulk of the gas is connected in some loose way with the constituents of the blood. Buxton's view is that it is probably associated moi-e or less closely with the albumins and albuminoids of the liquor sanguinis and corpuscles. He does not think that there is any destruction of red blood corpuscles. He reports having carefully watched the corpuscles in the web of a frog's foot while the frog was in a bell- jar of nitrous oxid, and was able to observe not only the phenomena of the circulation under these conditions, but also to satisfy himself that no breaking up of corpuscles was evident. The loose association which nitrous oxid is assumed to form with hemoglobin, as proved by the darkened color taken on by arterial blood when it is shaken with the gas, seems to indicate that nitrous oxid is able to displace oxygen in its chemical union in the blood. This combination of nitrous oxid with the constituents of the blood, if such actually occurs, is very unstable and very different from that produced by carbon monoxid, which is cumulative. Blood which has been saturated with nitrous oxid gives it up at once when left in free contact with oxygen or the air, and this has been used as a strong argu- ment against the acceptance of the formation of a compound, however loose it might be. This does not necessarily follow, for such conduct may readily be due to mass action, that is to say, both oxygen and * Brunn : Loc. cit. '■" Buxton : ' ' Ansestheties, ' ' 1907, 60. NITROUS OXID 129 nitrous ox id may form weak compounds with hemoglobin, the former being the stronger. Fresh hemoglobin will form compounds with the respective gases in proportion, not only in accord with the stability of the compounds, but in proportion to the relative quantities brought in contact with the hemoglobin. When the percentage of nitrogen mon- oxid in inspired air is very small it forms practically no appreciable amount of its loose compound, at least not a sufficient quantity to circu- late in the system to produce its physiological effects beyond those of exhilaration, i. e., intoxication. When the inspired gas contains only nitrous oxid the percentage will be rapidly diminished; in fact, almost as fast as the oxyhemoglobin in the blood is brought in contact with it. By regulating the proportions of the two gases brought into con- tact with the blood, it is theoretically possible to keep the oxygenation of the tissues going on as in normal life and at the same time secure the true physiological effect of the nitrous oxid. In maintaining these con- ditions another important factor enters in, namely, carbon dioxid. Yandell Henderson ^ has demonstrated that the carbon dioxid in the blood is a respiratory stimulant. Therefore, overventilation with oxygen is to be avoided. In advocating rebreathing of nitrous oxid-oxygen mixture, Gatch ^ claims that the beneficial effects are due to the carbon dioxid which comes from the expired air. His practice is to allow rebreathing until the percentage of carbon dioxid in the gas in the bag reaches four per cent; that is to say, the composition of ordinary expired air as far as carbon dioxid is concerned. For a more detailed treatment of this the reader is referred to the Chapter on Eebreathing. If the absorption is a phenomenon of simple solution — and that nitrous oxid displaces a certain amount of oxygen in the blood is gen- erally accepted by all observers — then the amount actually absorbed by the blood will depend upon the percentage composition of the mixed gases inhaled; that is, the partial pressure exerted by the gas in ques- tion. When nitrous oxid containing practically no free oxygen is inhaled the normal oxygen content of the blood is quickly diminished. If the percentage of nitrous oxid in the inspired gases is reduced to the minimum by discontinuing its administration, that which was ab- sorbed is quickly thrown out of the circulation by virtue of its vapor tension and oxygen takes its place, reproducing the normal conditions of the gaseous contents of the blood, as far as oxygen , is concerned. In the blood, according to the investigations of Klikowisch,^ nitrous oxid causes no chemical or morphological changes of any kind, but it is ' ' ' Acapnia and Shock, " " Carbon Dioxide as a Factor in the Eegulation of the Heart Eate, ' ' Am. J. Physiol, Feb. 1, 1908, SI, No. 1. ^"Nitrous Oxide-Oxygen Anesthesia by the Method of Eebreathing," /. Am. Med. Assn., March 5, 3910. ' Brunn : Loc. cit. 130 ANESTHESIA in the blood merely in the form of a physical solution. It is pro- portionately rapidly reexcreted on diminution of the partial pressure. Decomposition of the nitrous oxid in the blood into oxygen and nitrogen does not seem to occur. In the spectral analysis the behavior of blood that has been saturated with nitrous oxid is the same as that of blood containing oxyhemoglobin (Klikowisch;, Eothmann). This also goes to show that nitrous oxid does not enter into any stable chemical com- bination with oxyhemoglobin. Besides the short duration of the nar- cosis, the absence of after-effects likewise points in the same direction. The opposite view of Ulbrich is declined by Eothmann, who explains the divergent findings of Ulbrich as due to the employment of too highly concentrated blood solutions, causing the absorption bands to become wider and less distinct. Eeeently (1908) Hamburger and Ewing have expressed themselves in favor of the harmlessness of nitrous oxid for the blood. They found it to produce no permanent diminution of the hemoglobin, and no anemia, as well as no increased hemolysis. Although differences in the quantity of the hemoglobin and the red blood corpuscles may occur, they are of transitory character and devoid of surgical importance. The formation of reduced hemoglobin is not referable to the anesthetic, but to the associated asphyxia. An increase of the time of coagulation is common, but not invariably present. The experiments of Buxton ^ and later of Wood and Cerna ^ indicate that nitrous oxid exerts a direct action upon the heart itself, having little or no direct influence upon the vasomotor centers of the brain cortex. Kemp,'^ on the other hand, holds that nitrous oxid can hardly be said to exert a direct action upon the heart, the cardiac effects being much more apt to depend upon the amount of oxygen admitted than upon the nitrous oxid. For further data concerning the modification of the anesthetic by oxygen or by atmospheric air, see Chapter II, General Physiology. Blood pressure is always increased with nitrous oxid given alone. With a judicious use of air or oxygen nitrous oxid anesthesia may be continued for a sufficient time to permit of any ordinary surgical inter- vention with very little variation in blood pressure. Concerning the blood pressure, Goldstein's * findings showed a marked increase to be exceptional, in contradistinction to the usual belief that blood pressure rapidly undergoes an enormous increase in the first stages of the asphyxiation. His first experiments concerned asphyxia- tions with nitrogen and hydrogen, but a considerable rise of the blood ^"AnEBsthetics," 1907, 57 et seq. "Therap. Gas., Aug., 1890. ^Brit. Med. J., Nov. 20, 1897, 1482. * Brunn : Loc. cit. NITROUS OXID 131 pressure was likewise absent with nitrous oxid, although some increase was present. The blood pressure underwent no essential changes when dogs and rabbits were given, in addition to the nitrous oxid, a quantity of air sufficient for the avoidance of dyspnea. Effects Upon the Nervous System. — It has already been noted that the third distinct step in the evolution of knowledge concerning the physiological action of nitrous oxid had for its foundation the specific action of the agent upon the nervous system. The earlier experiments of Buxton, Wood and Cerna, and others, to which reference has already been made, confirmed the theory of the direct action of the gas upon the nervous system. Buxton,^ in observations upon this subject, found that, while asphyxia caused diminution of the bulk of the brain and cord, nitrous oxid produced so great an enlargement as to force out the cerebrospinal fluid. He referred these changes to a vasomotor origin, and held that they explained many of the nervous phenomena elicited in persons narcotized with nitrous oxid. The most natural inference, from the study of the reflexes and other effects upon the nervous system, is, according to Kemp,^ that nitrous oxid acts most powerfully upon the central nervous system, especially upon the brain cortex. The effect of nitrous oxid, when first inhaled, is a pleasurable exhil- aration, which varies with the individual, with the degree of dilution of the gas with oxygen or air, and with the method of administration employed. During this time the senses of the individual are rendered more acute ; this is followed by analgesia ; and then by anesthesia, during which last the patient is profoundly unconscious and insensitive to pain. Hallucinations, frequently of an erotic nature, often mark the hyper- esthetic stage which precedes anesthesia. These not infrequently persist after the complete return of consciousness. The practical and medico- legal significance of this phase of nitrous oxid anesthesia is easily apparent. Effects Upon the Muscular System. — It is a well-established fact that nitrous oxid does not usually induce muscular relaxation when adminis- tered alone. When oxygen deprivation is complete, and the administra- tion of nitrous oxid is continued, the limbs become rigid, the body some- times assuming the position of opisthotonos. Sometimes rhythmic tremors of the upper extremities are noted. The muscular manifesta- tions, other than general rigidity, are now seldom seen in nitrous oxid anesthesia, for the reason that it is practically never given alone, even for very short operations. For a further discussion of the muscular phenomena see Stages of Anesthesia, p. 59. Effects Upon the Glandular System and Other Structures. — Nitrous 1 Buxton: " Ansesthetics, " 1907, 62. ^Kemp: Log. cit. 132 ANESTHESIA oxid causes, according to Kemp/ a contraction of the renal vessels, so that urinary secretion is rapidly diminished. Inasmuch as nitrous oxid is not eliminated through the kidneys (see Chapter on Physiology, page 60), it would seem fair to assume that the gas exerts no unfavorable effect upon- these organs, and that the albuminuria sometimes reported is due to other causes. Involuntary micturition may occur during nitrous oxid anesthesia. The alimentary tract is not unfavorably affected by nitrous oxid unless its administration is pushed to an unnecessary degree. In such case there may be some nausea^ vomiting, and even involuntary defeca- tion. The untoward symptoms which accompany nitrous oxid anesthesia are generally ascribed to unnecessary deoxygenation rather than to any irritant or other quality of the gas itself. Causes of Death..- — When nitrous oxid is given pure, or alone, death is always due to oxygen deprivation or asphyxia. The heart continues to beat after respiration has ceased, which proves that death is not due to failure of circulation. (For further data concerning the effects of overdose, Avhich may lead to shock or to death, see Stages of Anesthesia, p. 59, and General Physiology, Chapter II.) Stages of Anesthesia. — The stages of anesthesia when nitrous oxid is used alone are rarely seen. Attempts have been made to separate the phenomena and to classify them under distinct stages, but this is impos- sible for the reason that it takes only from thirty seconds to one minute to reach full surgical anesthesia, the time elapsing between consciousness and surgical anesthesia being so short that these different degrees cannot be noted. Inasmuch as nitrous oxid is now so seldom given alone, but rather with air, with oxygen, or with the utilization of rebreathing, so that the duration of the anesthetic period can be prolonged at will, it is possible to note definite stages Just as is the case with other inhalation anes- thetics. The course of the anesthesia is smooth and practically feature- less, as is the case with the other agents, unless there is faulty technique somewhere. A leak in the apparatus, a mask that does not fit snugly, too much oxygen, not enough nitrous oxid, neglect of preliminary med- ication — any one or a combination of these errors of technique may convert a featureless narcosis into one marked by more or less disagree- able complications. Prom experiments upon lower animals it is known that too much oxygen or too little nitrous oxid may act as an overdose, with the same phenomena noted with an overdose of ether or chloroform. The iirst stage is marked by a subjective feeling of warmth in the lips, and a sort of numbness in the limbs and other parts of the body, quickly followed by a feeling of exhilaration, sometimes described as a ^Kemp: N. Y. Med. J., Nov., 1899. NITROUS OXID 133 "thrilling." This may be, and generally is, accompanied by the impulse to breathe more rapidly and more deeply. Tinnitus, a feeling of fullness in the head, and a "smothering" sensation, if the nitrous oxid is "pushed" too rapidly, precede the loss of consciousness. Objectively, it is noted that the respirations are quickened and deepened, the pulse grows fuller, and blood pressure is raised. Twenty to thirty seconds is the average duration of this stage, which may be said to end with the dis- appearance of coordination and consciousness. The second stage, or stage of excitem,ent, is initiated with the loss of consciousness. Incoherent thoughts and words and purposeless muscular movements, particularly of the arms and legs, are now apt to occur. The laughing, crying, muttering, and incoordinate movements vary with the patient. As may be imagined from the name, "laughing gas," ex- hilaration rather than depression is apt to mark the psychic phenomena of this stage. It is during this period that fanciful, sometimes erotic, dreams, which may persist after the return of consciousness, occur. The pulse is still full, and somewhat more rapid than during the first stage. The respirations are more rapid and deeper than normal, or than during the first stage in cases where the right proportion of air or oxygen is not given. Swallowing movements, and sometimes stertor, are noted. The pupils become dilated, and a twitching of the eyelids is often followed by their separation. The skin now assumes the duskiness or lividity which is generally a feature of nitrous oxid anesthesia, and which is more or less marked according to the normal complexion of the indi- vidual and according to the care with which the administration is con- ducted. Hearing continues during this stage. While the patient is unconscious, any undue roughness or careless treatment may markedly increase the excitement, aggravating all the phenomena noted. No surgical intervention should be attempted during this stage. The third stage, or the stage of surgical anesth esia, with perfect tech- nique, is induced in about sixty seconds to four minutes, the time vary- ing, of course, with the patient, with the purity of the nitrous oxid, and with the technique as regards the regulation of oxygen and other details. The stertorous, snoring breathing, with loss of rhythm, mentioned by many writers as marking the onset of the surgical stage of anesthesia, depends upon the method of administration, and especially upon the pre- liminary medication. Breathing should be automatic, regular, and with- out noise. The pulse is full and regular, and slightly increased in rapid- ity, from 80 to 90, though it may be normal. The lividity previously noted should not be increased in degree as anesthesia advances. The lid and other reflexes are abolished, and muscular relaxation is more or less complete, according to the purpose of the anesthesia and the technique employed. In order to maintain this stage of surgical anesthesia, it is important 134 ANESTHESIA not to give too much ox3^gen or too much nitrous oxid, Avith a corre- sponding increase or decrease of the other gas. The time required to reach this stage is so short that an inexperienced administrator may allow the patient to "come out" or to go on to the stage of overdose. In this connection it is to be borne in mind that nitrous oxid is stimulat- ing, and that the patient must not be allowed to return to the second stage, or the stage of hypersensitiveness. The automatic breathing, with or without stertor, the widely dilated or contracted pupils (varying with the preliminary medication), full and regular pulse, with a slight degree of cyanosis, indicate the third stage. Two or three stertorous respirations indicate complete anesthesia. The fourth stage, or stage of overdose, supervenes through some error of technique by which asphyxia becomes the predominant feature of the narcosis-. Breathing becomes embarrassed, usually through convulsive muscular spasm. The interference with respiration is first marked by hyperpnea (excessive breathing), then by dyspnea (difficult breathing). Violent or convulsive expiratory efforts, sometimes accompanied by gen- eral muscular spasms, mark the second stage of asphyxia. Following this there is a stage of exhaustion in which muscular spasm is super- seded by muscular flaccidity. The pupils become more widely dilated, the lids are widely open, the conjunctivae are insensitive, the pulse be- comes imperceptible, respiration is marked by prolonged sighing inspira- tions, which gradually cease. Paralysis of the respiratory center is com- plete, and death supervenes. Marked cyanosis accompanies this condi- tion of affairs. Interference with the passage of the blood through the pulmonary and systemic vessels, and accumulation, in consequence, of blood in the right side of the heart and in the systemic veins, with the circulation, in all parts of the body, of deoxygenated blood, explain the eventuation of the stage of overdose in nitrous oxid anesthesia. This stage of anesthesia may be rendered more liable by certain preexisting conditions, which are discussed under Contraindications. The length of time before it eventuates in death varies with the sub- ject. It may be noted that the time required to reach full surgical narcosis is from thirty seconds to four minutes, varying with the patient; that the available period for operation depends entirely upon the technique employed, ranging from thirty seconds to hours; and that the recovery period, when asphyxial symptoms do not occur, is completed in five min- utes or less from the time the mask is removed. Elimination. — The rapidity with which the blood will rid itself of nitrous oxid has been made the subject of study by Kemp,^ who found, in animal experiments, that in less than two minutes the quantity of nitrous oxid in the blood fell from over twenty per cent to six and nine- ^Kemp: Brit. Med. J., Nov. 20, 1897, 1480. NITROUS OXID 135 tenths per cent. The normal rapid recovery of patients, he holds, is quite in accord with these findings. It has already been noted that nitrous oxid is not eliminated ])y the kidneys. The lungs furnish the channel of elimination of nitrous oxid. After-Elf ects. — As already stated, there are less after-effects with this anesthetic than with any other. The only possibility of after-effects is when the subject is nnsuited for this particular form of anesthesia; or when an irregular narcosis has been given ; or when the nervous system is so upset for any reason that the least excitement is cause for anxiety. The Lancet of March, 1902, mentions a case in which, after a few min- utes' inhalation, the patient remained practically asleep for four days. The undesirable patients so often referred to, that is, men with powerful build, are sometimes temporarily unbalanced after a short administra- tion. Again, those with weak hearts may have slight pallor, feebleness of pulse, and faintness; as a general rule, however, all of these things are conspicuous by their absence. COMPARISON WITH OTHER AGENTS In the earlier period of nitrous oxid history this agent was hardly comparable with other inhalation anesthetics, inasmuch as it was not considered a true anesthetic. With modern methods, however, this no longer holds. Nitrous oxid is considered as truly an anesthetic as is ether or chloroform. Given with oxygen it ranks above either so far as safety to life is concerned. In point of after-effects it takes precedence over all other agents, since it is practically free from sequelae if admin- istered with a fair degree of care. Nitrous oxid and ether, with enough oxygen to prevent cyanosis, is the safest inhalation anesthetic, both as to life and after-effects. INDICATIONS AND CONTRAINDICATIONS Nitrous oxid alone is very limited in its indications. In fact, at this stage of development of methods of administration it is never indicated. It is distinctly contraindicated, even for very short operations, in young children (under four years), because of their immature musculature, which makes breathing in the bag difficult for them. It is also distinctly contraindicated with old persons, or persons with a generally weakened musculature, and in adults of whatever age whose arteries are sclerosed. Advanced phthisis, valvular disease, and women during any of the physi- ological epochs, when nervous and mental phenomena are apt to be easily exaggerated, present contraindications to the use of nitrous oxid alone. When this gas is judiciously employed, with the careful admission of 136 ANESTHESIA oxygen, the contraindications are modified. It is still contraindicated for children, because these patients take any anesthetic poorly with a closed method. (See Chapter VIII, Selection of Anesthetic.) For- strong, muscular, athletic, alcoholic and obese subjects, or per- sons with any obstruction to the air passages, such as enlarged tonsils, adenoids, etc., and for ophthalmic surgery, nitrous oxid is contraindi- cated, unless employed with the utmost skill. ADMINISTRATION Before discussing the different methods of administration it might be well to pause and consider a few necessary details. Heating the Gas. — This is accomplished in several ways : ( 1 ) by an alcohol lamp, .with a coil for the gas going through the upper portion of the heater, as in the Teter apparatus (see p. 152) ; (2) by a coil from the tank being placed in a hot water cup, as in the Gwathmey anesthetizer (p. 150); (3) by passing the gas through a coil contained in a metal cylinder filled with thermal salts, as used by Griffith Davis (see p. 148) ; (4) by passing the gas over water electrically heated (see p. 424). The gas should be heated to the temperature of the body. Heating the gas admits of its uniform diffusion through the alveolar walls and usually enables the administrator to secure surgical anesthesia before the asphyxial signs occur. Essential Features of Any Satisfactory Method or Apparatus. — All apparatus should embody the four fundamental principles underlying the successful administration of nitrous oxid and oxygen, that is to say, valvular and rebreathing, warmed vapors, moisture regulation of the pressure, and addition of other anesthetics when needed. Apparatus for Administering Nitrous Oxid Alone or with Air. — All that is necessary for the administration of the gas alone is a tightly fit- ting mask, with valves which may be thrown out of use when rebreathing is to be utilized. To this mask a rubber bag is attached. Eubber tubing connects the bag with the gas cylinder. When air is added to the nitrous oxid an extra valve may be used to allow definite proportions of air. Dangers of Administration of Nitrous Oxid Alone. — The majority of fatalities have occurred with the administration of nitrous oxid alone, and given through valves. Of these fatalities the greater number were men in robust health or alcoholics. Nitrous oxid has no toxic effect as have chloroform and ether. Death occurs as a result of asphyx- iation. The only possibility of a death by asphyxiation is the inability of the administrator to differentiate between asphyxial and anesthetic signs. Whether it is administered alone, with air or with oxygen, the anes- NITROUS OXID 137 thetist should be careful to keep a clear airway and see that no asphyxial symptoms occur at any time. Recognition of Asphyxial Symptoms. — Embarrassed respiration, ir- regular, shallow, and jerky, is an asphyxial symptom. This may or may not be accompanied by stertor. The fingers and muscles of the arms and legs are thrown into clonic spasms, which quickly develop into tonic spasms with rigidity and muscular contraction of the muscles of the neck and chest. There is marked cyanosis. Eyelids may or may not be closed, but are usually open with lid reflex present. The respiration ceases. If at this point the mask is removed, in the vast majority of cases the patient comes out of this state apparently none the worse for the experience. The heart will always be found beating slowly and regu- larly, even after cessation of respiration. If, however, the mask is held rigidly in place at this point, so that the next long, deep breath is gas instead of air, a cessation of all the vital functions is apt to cease immediately. No administration of nitrous oxid should be attempted unless the anesthetist is prepared for a tracheotomy. Administration of Nitrous Oxid Alone. — If given in this way, with- out mixture of air or oxygen, and without heating, it must necessarily be for short operations, and it must be given to the point of asphyxia- tion, then discontinued and administered again. This is the most dan- gerous way in which to administer the gas, and should never be attempted except in emergency cases or as a sequence. It is true that patients have been anesthetized in this way for short operations with a resulting fatality that is almost negligible; nevertheless, 90 per cent of all fatalities have occurred when the gas was thus administered. Administration to Asphyxiation with and without Valves.: — A crude method, practiced by many dentists, is to administer the gas to the point of asphyxiation, remove the mask, and make the extraction. Use of Expiratory Valve Alone. — Another method is to use the ex- piratory valve alone, thus allowing to-and-fro breathing from the first, and increasing the pressure until full anesthesia ensues. This requires more gas and a little longer time, but it is almost as valuable as washing out the lungs by the valvular method, and then switching to to-and-fro breathing. It is preferable to using valves alone. Administration without Valves. — The third method of giving the gas is without any valves, by allowing the gas to flow in the mask and simply increasing the pressure in the bag and allowing the surplus to escape under the margin of the mask, and continuing to increase the pressure until ingress of air between the face and the mask is impossible, and full anesthesia is secured. This is a makeshift, and a wasteful method, but it may be well to know that anesthesia can be satisfactorily induced in an emergency in this way. Precautions When Administered Alone. — Whenever the gas is ad- 138 ANESTHESIA ministered alone, as for the extraction of a tooth or the opening of an abscess, it is always best to have some method of switching from the valves to to-and-fro breathing. With some patients the asphyxial point Fig. 26. — Guedel's Apparatus for the Self-administration of Nitrous Oxid and Air. Apparatus attached to cylinder. (1) Stopcock controlling flow of gas from supply bag. (2) Respiratory valve. (For detail see Fig. 27.) (3) Flexible rubber nose mask without valves. Valves are removed to body of apparatus so that mixture of gas and air can be regulated without disturbing the patient. (4) Metal band with hook for hanging apparatus to operating chair or table. In obstetrical work the ap- paratus is placed on its side on the bed. (5) Hollow metal handle for nose mask. Patient holds mask. will be reached before true anesthesia occurs. This is the principal objection to the administration of nitrous oxid alone. When adminis- tered only part of the time through valves, the anesthetist should make the change before the asphyxial signs occur, and deepen the anesthesia NITROUS OXID 139 by simply holding the mask in position and allowing the patient to breathe back and forth in the bag. The advantages gained by this method are that it is safer and also gives a deeper and longer period of available anesthesia Vi^ith a smaller amount of gas; the after-effect will also be less. In fact, by closing either the mouth or nares, thus compelling the patient to breathe through the one open airway, and using this airway for the administration, a satisfactory anesthesia has been induced by inserting the rubber tube from the gas tank and grad- 3— — m^^^L I — jE^^y ■ S^^HIflS^' ' k. '" ' ' 1 1 \ ml Fig. 27. — Guedel's Apparatus, Showing Detail Construction of Respiratory Valve. (1) Expiratory openings. A disc prevents the entrance of air during in- spiration and permits the escape of part of the expired gases during expiration. (2) In- spiratory openings for admitting air which is mixed with the inspired gas. (3) Screw for regulating percentages of inspired air. (4) Screw limiting movements of disc for regulating amount of gas rebreathed. (5) Graduated dial showing percentages of air inspired. ually increasing the pressure. This is a wasteful method and is not advocated. In all cases there should be some means of heating the gas before it reaches the patient. Guedel has perfected an apparatus for the administration of nitrous oxid alone, and especially for the use of the analgesic stage of nitrous oxid. He recommends it specially for confinement cases. His cylinder of nitrous oxid is placed within convenient reach of the patient. The patient takes the apparatus and places it over the nose or mouth and inhales until the anesthetic stage is reached, when the hands drop to the side. It is also used by dentists for the analgesic stage of anesthesia. 140 ANESTHESIA The apparatus is commendable in that it is very simple and inexpensive. (See Figs. 26 and 27.) Administration of Nitrous Oxid with Air in Unknown Quantities. — The continuous administration of nitrous oxid with enough air to pre- vent asphyxial symptoms places a severe tax upon the anesthetist's resources. With selected subjects and under proper conditions a safe and even plane of anesthesia can be maintained. Directions. — (a) With valves alone: Place the mask in position and induce anesthesia as stated above. When stertor, irregular breathing, or automatic breathing announces surgical anesthesia, raise the mask for one respiration, then reapply and hold in position for from three to ten respirations, according to the patient, when another breath of air is given, and so continued. (b) With valves and to-and-fro breathing: This method is better for the patient, keeping the pulse nearly normal, respirations deep and full, with better muscular relaxation, and is an easier anesthetic to maintain. In getting the patient under, the following procedure is usual : (1) If the apparatus will allow, have the patient breathe air through the valves before turning on the gas. (2) Turn on the nitrous oxid and allow the patient to breathe through valves from three to seven times. (3) Now have to-and-fro breathing for as many times. (4) Eeturn to valves for three to seven breaths. (5) Now have to-and-fro breathing as before. This alternating from valves to to-and-fro breathing will occupy from forty seconds to a minute and a half, when the patient will be found to be deeply under the anesthetic. If, now, the operation is to last for one hour or more, either the above or the following method can be used after surgical anesthesia has been established. Use the expiratory valve alone, allowing a small but regular flow of the gas at all times, thus keeping the bag fairly distended by having rebreathing constantly and removing the mask whenever the stertor or other asphyxial signs become too marked. This method is especially useful for alcoholics and athletes, and all other patients in which a posi- tive pressure is indicated. The above method has also been successfully employed in nose and throat work, using the nosepiece with expiratory valve and having a stopcock between the nosepiece and bag for an occa- sional breath of air. By regulating the expiratory valve any amount of pressure can be maintained in the lungs. This method of anesthesia can be kept up indefinitely, and is especially useful in adenoid and tonsil cases. This rebreathing, together with the expiratory valves, can be more NITROUS OXID 141 readily maintained when used as a sequence to the drop method of etlicr (p. 204), when the patient has been under the influence of the ether for ten to fifteen minutes, or toward the close of any operation lasting one hour or more. The Administration of Nitrous Oxid with Definite Amounts of Air. — Hewitt has made a number of experiments to determine the exa<;t per- centage of nitrous oxid suitable to be administered with air. The fol- lowing are the net results of these experiments : The best definite mix- ture for men is from 14 to 18 per cent of air; for women and children, 18 to 23 per cent of air. If, during an administration of nitrous oxid with air, the supply of oxygen gives out, anesthesia can be continued by pushing back the bag containing the oxygen so that air can be admitted through the valve and allowing a continuous flow of from 14 to 22 per cent of air with the nitrous oxid. The best method of administration is for the anesthetist to be able to use the valves, and also switch to to-and-fro breathing at any time during the administration. Whenever, for any reason, no oxygen is at hand, it is necessary, if a continuous flow of air through the valves is to be allowed, that the apparatus is so arranged that the air supply is independent of the nitrous oxid. Directions. — Anesthesia is instituted as follows: Place the index to the air valve so as to allow an intake of 25 per cent of air. Allow the full intake of nitrous oxid through that valve. After two or three inspirations, cut down the air intake to between 14 and 22 per cent. Turn the nitrous oxid valve so as to allow rebreathing continuously. From this time on the index to the air valve must be changed to suit the requirements of the case. If positive pressure is indicated, this can be accomplished by tightening the screw on the expiratory valve so that very little air escapes, at the same time increasing slightly the flow of nitrous oxid. In order to determine approximately the percentage of air being used, the flow of nitrous oxid must be an even one. Occa- sionally it will be necessary to cut off the air entirely and have to-and-fro breathing until the anesthesia is satisfactory; then return to the valve and continue. This form of anesthesia is especially useful as a sequence after surgical anesthesia has been maintained for thirty minutes or more, when, for any reason, the chloroform and ether should be reduced to a minimum. Nitrous Oxid as a Sequence to Ether. — Wlien nitrous oxid is used as a sequence to ether the reflexes should be allowed to become active before instituting the change. With the chloroform-ether-nitrous oxid sequence the reflexes should be very active and the change be made grad- ually; that is to say, allow rebreathing in the bag before turning on the nitrous oxid. Even in laparotomies, where absolute relaxation is required, after anesthesia lias been maintained for thirty minutes or 142 ANESTHESIA more, this method can be successfully substituted. This reduces the amount of ether or chloroform to a minimum, and, there being less strain upon the kidneys and lungs, the after-effects are reduced to a minimum. Nitrous Oxid with Air. — As previously stated, when nitrous oxid and air are used as a sequence, the maintenance of an even plane of anesthesia is so easy and, at the same time, satisfactory that the descrip- tion of the technique of this sequence is worthy of a place by itself. Technique of Ether-Nitrous Oxid (Air) Sequence. — If ether by the drop method has been used and a change to nitrous oxid is desired, allow the reflexes to become slightly active; place the mask upon the face and turn to to-and-fro breathing, the bag being two-thirds full of the nitrous oxid. Note the results, and increase the pressure in the bag to intensify the anesthesia, or, if the anesthesia is satisfactory, main- tain it by either of the methods already outlined. When the reflexes are abolished slight cyanosis sets in, and the anesthesia is now changed to one of nitrous oxid and air. When this occurs remove the mask when- ever necessary for one inhalation or more, and then repeat, allowing the gas to flow in the bag slowly but regularly. If, however, the patient is very lightly under, allow breathing through valves for three to eight respirations, turn to to-and-fro breathing, then allow one to two breaths of air, and then return to the gas. Allow air whenever the reflexes are entirely abolished and cyanosis is marked and breathing stertorous. Technique with A.C.E. — The technique with chloroform-ether, or the A.C.E. mixture is as follows : Allow the eyelids and other reflexes to become somewhat active ; place the mask upon the face as the patient exhales, the mask being arranged for to-and-fro breathing, but the bag empty. Eemove the mask from face, allow patient one breath of pure air, and replace mask so that the exhalation enters the bag. Continue thus, alternately raising and replacing the mask until the bag is filled. When this occurs hold the mask in place. If reflexes are now abolished raise the mask and allow one breath of air and thus continue until reflexes begin to get quite active again. When this occurs turn on gas slowly, alloAving rebreathing until they are lulled or abolished. Advantages of Ether- (or Chloroform-Ether) Nitrous Oxid Se- quence. — By instituting nitrous oxid anesthesia after any operation that has lasted at least one hour, the following results are accomplished : A non-poisonous ^ anesthesia replaces a poisonous one at a time when a stronger anesthetic is capable of doing the greatest damage. The resisting powers of any individual at this time being reduced to a mini- ^ The term non-poisonous is here used in a restricted sense as compared with chloroform and ether, which are active poisons to both the nerve and muacle fibers. NITROUS OXID 143 mum, the kidneys, lungs, and otlior parenchyma are thus possihly saved the coup de grace. Nitrous oxid and air fulfil all demands at this time, the relaxation required being easily maintained. The Advantages of Administration of Oxygen with Nitrous Oxid. — When oxygen is used with nitrous oxid, a safer, deeper, and more satis- factory anesthesia is obtained than is possible with air. When the nitrous oxid is heated and supplemented by warmed moist ether, when necessary, we have the best form of anesthesia, considered from every standpoint, available to-day. Those who have never used oxygen with nitrous oxid, and who have acquired the technique of administering it alone, will be surprised by the ease and latitude given by this combina- ■ tion. One of us (J. T. G.) has given several anesthesias lasting for two hours and more with nitrous oxid and oxygen without the aid of ether, chloroform, or ethyl chlorid, and in one instance the anesthetic was not preceded by any preliminary medication. With adults the preliminary medication gives a wider latitude to the anesthetist than if this were not used. When the subject is well selected, and the administration properly conducted, a slight increase in the percentage of oxygen being allowed from time to time as the operation proceeds, the mechanical breathing, color, and reflexes, together with the relaxation required, are sufficient guides for our use. The pulse and respiration will usually be normal, except when stimulated by the operation. If loud stertor commences or increases it is a sign for more oxygen. If muscular twitches are observed at any time this also is an indication for more oxygen. In anesthetizing children under ten years of age, after surgical anes- thesia is reached, it is best to raise the mask slightly from the face, about one-eighth of an inch, and allow the little patient to breathe the com- bined gases by having a plus pressure in the bag at all times, or by keeping the expiratory valve open and allowing rebreathing constantly. Weak, anemic men and middle-aged women can be successfully anes- thetized with nitrous oxid and oxygen alone, provided the valves and rebreathing are used discriminately. With a vast majority of patients it is safer to supplement the nitrous oxid and oxygen with small amounts of ether. Superiority of Oxygen Over Air. — The objection to using air is that it contains a large percentage of nitrogen which is useless for anesthetic purposes. Hewitt has illustrated this in the following manner : When air is given the equation could read like this : .. ,, , , ._ ^ S 8 per cent oxygen Air (by volume), 40 per cent = i r,,^ . •, (62, per cent nitrogen Nitrous oxid 60 per cent = 60 per cent nitrous oxid This mixture, containing eight per cent of oxygen by volume, would be the proper amount as far as the oxygen is concerned. Sixty per cent 144 ANESTHESIA of nitrous oxid would be insufficient to produce tranquil anesthesia. By- using oxygen instead of air in the above equation we are able to replace the thirty-two parts of useless nitrogen by a corresponding quantity of useful nitrous oxid, the percentage of oxygen remaining the same. The equation would now read like this : Oxygen = 8 per cent (by volume) Nitrous oxid = 92 per cent (by volume) This is about the average used with adult patients, and is perfectly satisfactory. Administration of Nitrous Oxid with Indefinite Quantities of Oxy- g-en. — Willis D. Gatch, formerly of Johns Hopkins Hospital, Baltimore, deserves the credit of emphasizing and placing upon a scientific basis the value of rebreathing. His apparatus consists — besides the cylinders Fig. 28. — Diagrammatic Sketch Showing Simple Method of Administering Nitrous Oxid and Oxygen with Indefinite Quantities of the Agents Used. 01 gas and oxygen, and connections — of one rubber bag, face-piece, and a two and a half-inch pipe connecting face-piece and bag. His mask con- sists principally of a rubber cuff, which is turned down over the ordinary mask so as to grasp the chin, cheeks, and nose of the patient. The patient may be made to breathe air or gas through valves or to-and-fro breathing into the bag. The main features of his apparatus are as follows : (1) It is simple, light, and easily portable. (2) It may be quickly sterilized by boiling. (3) There is economy in the use of gas. Gatch's Method of Administration.— "With the air-vent open, the cuff of the mask is fitted to the patient's face, care being taken to prevent NITROUS OXID 145 the admission of air at the sides of the nose. In some cases it may be necessary to lay a piece of gauze across the bridge of the nose and draw the cuff over it, or to hold the cufE there with the finger. The inner tube of the valve-box is pushed to its mid-position and nitrous oxid admitted to the bag. The patient now inhales this gas and expires into the outer air, thus washing out, as it were, all the air from his lungs. This process is continued until he becomes very slightly cyanotic. Then the inner tube is pushed to its final position and the patient breathes to-and-fro into the bag. At this moment a small puff of oxygen is admitted to the bag, just enough to restore the natural color of the face. The patient now rebreathes a mixture of nitrous oxid and oxygen until the inner tube of the valve box is moved back to its mid-position. He then ex- hales each breath into the air until the bag is empty. The anesthetizer then fills it with a fresh mixture of gases, which the patient again re- breathes. No attempt is made to measure the exact percentage of oxygen given. This we regard as unnecessary. It is perfectly easy to add directly from the oxygen cylinder exactly the right amount of this gas to each bag of nitrous oxid. The patient's color is an ex- tremely delicate indicator of the amount of oxygen he is getting. Our rule is to give just enough oxygen to keep the patient's color free of the least tint of cyanosis. The most elaborate device for reg- ulating the percentages of the two gases can do nothing more than this." All that is needed to success- fully maintain surgical anesthesia with nitrous oxid and oxygen by the above method is any ordinary accurately fitting face-piece, and a mask with valves that will also allow rebreathing when indicated, and a rubber bag. Any inhaler used for the gas-ether sequence can be utilized to give gas and oxygen by the Gatch method. The stopcock at the end of the bag may be replaced by a Y-shaped connection having tubes lead- ing respectively to the nitrous oxid and oxygen tanks. The bag is to Fig. 29. — Davis Nitrous Oxid-Oxygen Apparatus. ' Fig. 30. — Davis Apparatus Case. — Contents: two 100 gal. cylinders of nitrous oxid, one 40 gal. cylinder of oxygen, thermic apparatus, and one two-bag gas-ether-ox\- gen inhaler. Fig. 31.— Davis Nitkous Oxid-Oxygen Apparatus with Vapor Apparatus Disconnected. Fig. 32. — Davis Nitrous Oxid-Oxygen Apparatus Showing Heater. Fig. 33. — Davis Nitrous Oxid-Oxygen Apparatus with Gwathmey Vapor Inhalee. •ifar n 1 1. - . -l';-:' J IF 1 j s Fig. 34. — Davis Nitrous Oxid-Oxygen Apparatus with Gwathmey Vapor Inhaler. Same as Fig. 33 with cover. Fig. 35. — Davis Nitrous Oxid-Oxygen Apparatus with Gwathmey Inhaler. Same as Fig. 31 without cover. ^ ^^1 ilJIH| ^^IRA& uH ^^^^^^^^^^^M^*^ ^H^HF i^^^lHI HH Fig. 36. — Coburn's Apparatus with Anesthetic Table and Cylinders Attached. ReBRCATMfNG Ba Fig. 37. — Coburn's Apparatus: Face-Piece and Bag. Fig. 38. — Coburn's Apparatus: Face-Piece and Electric Heater. Fig. 39. — Gwathmey's Nitrous Oxid-Oxygen Apparatus. NITROUS OXID 151 be kept filled with nitrous oxid, and a puff of oxygen is given whenever indicated by cyanosis or active reflexes. While this apparatus has been used in thousands of cases with satis- factory results, from the descrij^tion of the apparatus and the method of administration given above it can be readily perceived that, unless the strictest attention is given to the administration, flaws will occasionally occur to mar the flxed plane of anesthesia that is to be aimed for. A possible objection outside of this consideration is the fact that the gases are not warmed except by the rebreathing of the patient, although they are thus properly moistened. Davis' Method.— Griffith Davis' apparatus embodies all the good features of the Gatch apparatus, and, in ad- dition, all the nitrous oxid is passed through a warming apparatus before it enters the mixing chamber. Coburn has devised an ap- paratus for the administra- tion of nitrous oxid and oxy- gen, according to the princi- ples enunciated by Gatch, but with the addition of an elec- trical heating apparatus for warming the gases. Coburn's hospital stand is very neat and compact. Methods of Administra- tion with Definite Quantities of Nitrous Oxid and Oxygen.— Hewitt's Method.— Hewitt's apparatus consists of two bags, one of which is used for nitrous oxid and the other for oxygen; and a mask with valves, cylinders, and connections. Hewitt's technique consists in administering the gases in the following manner : "The bags are half filled with their respective gases. When the gas is turned on, nitrous oxid and a small percentage of oxygen gain admission to the lungs. - The bags are kept as nearly equal as possible in size, and partially distended throughout. The percentage of oxygen is gradually increased as the operation proceeds, but also occasionally admit a breath of fresh air." Hewitt limits the class of patients suit- FlG. 40. GWATHMEY OxYGEN Y-PiECE Adaptedf or Bennett's, FuRNiss', OR Gwathmey's In- haler. ^v ij Fig. 41. -Teter Nitrous Oxid-Oxygen Apparatus. NITROUS OXID 153 able for this apparatus to weak, anemic men and middle-aged women. His experience with this apparatus has not been such as to recommend its general adoption. Gwathmey's Method.— The Gwathmey apparatus (Figs. 39 and 40) is a modification of Hewitt's with the valve on the nitrous oxid bag so arranged that rebreathing can be instituted at any time. Ether can also be added when necessary, and the nitrous oxid is heated by Brown's hot-water coil and cups. Ethyl chlorid can be given with the nitrous oxid and oxygen, if needed. The ex- piratory valve is regulated by a screw. Free expirations or forced expirations can thus be instituted at will by the anesthetizer. The technique is about the same as with the Teter apparatus. Teter^s Method. — One of the best ap- paratus yet devised for the administration of nitrous oxid and oxygen for all purposes is the apparatus invented by Charles K. Teter, of Cleveland, Ohio. All the vapors inhaled by the patient are warmed and can be given through valves, or by the method of rebreathing, or a combination ot these two methods, and at normal or positive pressure. The bags for the gas and oxygen are separate, and a definite amount of oxygen is constantly being mixed with the nitrous oxid. A certain amount of the expired gases is also constantly escaping through the expiratory valve. Warmed ether or chloroform can be added when needed. A more even plane of anesthesia is possible with this apparatus than with any other. A valve is placed upon the oxygen bag, but not upon the nitrous oxid, which allows continuous to-and- fro breathing. The following is the technique as given by Dr. Teter for the usual administration, and also for the administration through the nose. Technique. — "Fill the nitrous oxid bag about two-thirds full; fill the oxygen bag so that it is pretty well distended and is under a little pressure. Just before placing inhaler over the patient's face, open the valve from the nitrous oxid bag. Now place inhaler in posi- tion, being sure that you have perfect coaptation to exclude all air. Start the nitrous oxid flowing from the cylinder into the bag; this should be so regulated as to keep this bag full all the time. After the patient has been breathing the pure gas for about ten to fifteen sec- onds, the oxygen valve should be opened to the second notch (which Fig. 42.— The Teter Vapor Warmer. 154 ANESTHESIA will be shown on the side of the valve cap and indicated by the ratchet), then keep increasing this one notch at a time, after three or four in- FiG. 43. — Tetbr's Face-Mask. halations, until you have reached the fifth or sixth notch; do not turn this any further unless there are symptoms of asphyxia manifested. (The first manifestation of asphyxia would be blue- ness of the features, which would be noticed first in the mucous membrane of the lips, in the ears and eyelids). If there are asphyxial symptoms pres- ent, you should advance the oxygen valve still far- ther forward. It will be necessary to start the oxy- gen flowing from the oxy- gen cylinder into the bag after the patient has been breathing the mixture about forty seconds, in or- der to keep this bag well distended at all times, otherwise you would not be receiving the amount of oxygen indicated or desired. In order to keep the oxygen bag well dis- tended the oxygen is allowed to flow very slowly from the cylinder, so Fig. 44. — Teter Ether Attachment. NITROUS OXID 155 slowly that one will not be able to hear it, but enough to keep tlie bag well distended all the time. Practice is the only sure teacher, but one is soon able to adjust this properly. "If your patient is not going under the effects of this mixture after Fig. 45. — Teter Nasal Inhaler. he has been breathing it for about forty seconds or less, he is inhaling too much oxygen, or there is an admixture of air. If the latter is the case, correct it; if the former, turn the oxygen valve back a notch or two for a few seconds, and, if he still does not respond, it may be that the oxygen is flowing too fast from the cylinder; if so, correct this, and your patient should pass into a sound and peaceful sleep. Of course, you will find some few patients that are exceptionally hard to Fig. 46. — Teter's Auxiliary Tube for Administering Nitrous Oxid and Oxygen Through the Mouth. Used in connection with the nasal inhaler. anesthetize, but by persistence all patients can be anesthetized with nitrous oxid and oxygen. "By fjlose observation on your part and being able to diagnose symp- toms properly in order to know when to increase or decrease the amount of oxygen, you are enabled not only to induce any desired depth of narcosis, but are able to maintain it for any reasonable length of time Fig. 47. — Teter Nitrous Oxid-Oxygen Apparatus with Nasal Inhaler in Use. Fig. 48. — Teter Nitrous Oxid-Oxygen Apparatus with Nasal Inhaler in Use, WITH Surgeon Operating. NITROUS OXII) 157 w without ever admitting one breath of atmospheric air. In fact, you will be able to obtain and maintain better anesthesia without the admit- tance of air. You should not cause any jactitation of the muscles, or .much if any cyanosis in producing anesthesia. . . . Do not be in too much of a hurry in bringing your patient under the influence of any anesthetic agent, but take some little time and give the system time to accustom itself to the new order of things. You will not only get much better results, but you will cause the anesthetic to be much safer by so doing." Technique to be Followed in Administering- Nitrous Oxid and Oxy- gen with, the Teter Apparatus and the Teter Nasal Inhaler. — "Fill the respective bags as stated under the heading, 'Technique for the proper administration of nitrous oxid and oxygen when the face inhaler is to be employed.' Open the valve from the nitrous oxid bag, then adjust inhaler, taking the thumbs and spreading the lower part of rubber cap so that this will not press upon the alae of the nose, tending to close the nostril. This inhaler is so constructed that by proper adjustment it will fit any nose. In small children the top may be up as high as the forehead, but this will not matter so long as all air is ex- cluded. "After adjusting inhaler, instruct the patient to breathe through the nose. If he will not do so, hold a piece of rubber over the mouth. (A quarter of a rubber ball the size of a large orange makes the best thing pos- sible for this purpose.) Now allow the nitrous oxid to flow continually so as to keep the nitrous oxid bag full. After the first few inhalations turn the valve from the oxygen bag to the second notch and gradually in- crease this to the fifth or sixth notch, as the symptoms will indicate. After about one-half minute you should start the oxygen to flowing from the cylinder into the bag very slowly, so slowly that you will not be able to hear it, but enough to keep this bag well filled all the time. Fig. 49. — Teter's Nasopharyn- geal Tubes for Nitrous Oxid AND Oxygen. 158 ANESTHESIA "After inducing the desired depth of anesthesia, which should be accomplished in about two minutes, remove the rubber from the mouth. If the patient breathes through the mouth release the plunger in the inhaler, and it will descend upon the exhalation disk. This is done by loosening a set screw, which normally holds this plunger up and away from the exhalation disk. The inhaler is to be held firmly in position. Fig. 50. — The Ohio Monovalve. Shown with warming device, including ether or chloroform cup. Now the nitrous oxid is turned on more strongly from the cylinder, and the pressure thus formed in the bag will force the nitrous oxid through the nose, and, although the patient is inhaling and exhaling through the mouth, he is compelled to breathe the nitrous oxid, as it is under pressure greater by far than the atmospheric pressure. The oxygen bag is also allowed to fill with oxygen, and this is forced along with the nitrous oxid, according to symptoms indicating its need. "It is out of the question to expect to maintain as tranquil an anesthesia by this method as is possible where we can exclude all at- NITROUS OXID 159 mospheric air and are not hampered in applying our agent, l)ut we can keep our patient under the anesthetic for any length of time and free from all physical pain. "If the patient continues to breathe through the nose, all that is necessary is to regulate the oxygen in accordance with symptoms dis- played and continue to the completion of the operation." Nitrous Oxid-Oxygen Endopharyngeally. — Connell has developed a very satisfactory method of administering nitrous oxid and oxygen, the technique of which is as follows : After the patient is surgically saturated with the anesthetic, the delivery is shifted to the pharyngeal method by the nasal route. Each nostril is plugged by a collar of thick rubber tubing slipped over the nasal cathe- ters. The pharyngeal rebreathing tube is then inserted, to which is attached a re- breathing bag. The quantity found most useful with this method is eight liters per minute, beginning with a five per cent oxy- gen mixture and increasing gradually up to a nine or ten per cent mixture by the end of the first hour. Where surgical relaxation is desired and protection against subconscious suffering is indicated, this is to be obtained not by dangerously increasing the oxygen starvation, but by adding ether as indicated. The rebreathing is used solely for economy. If the pharyngeal delivery is 22 liters, or five and one-half gallons, a minute, rebreathing may be dispensed with if the mouth be kept closed. (See Connell's Anesthetometer, p. 160.) The Ohio Monovalve. — The gas pressure as it leaves the cylinders is auiomaiically reduced and controlled here. In preparing to give the anesthetic, a cylinder of nitrous oxid and oxygen are both opened as far as the valves will permit. The gas passes through regulators which reduce the pressure to about two pounds, then through automatic valves, where it is further reduced to breathing pressure. The bags fill automatically, but when they are full the gas stops flowing. The bags are refilled as fast as the gas is con- sumed. There is only one valve to handle. With it, pure nitrous oxid is given, and when it is turned beyond a certain point oxygen is mixed 1^ mW^Fr^ T iT^ .-%:' h^ i5^^=U* 1 1 I bB 1 B l^B wk ^B^^ J 1^ 1 B I 9^W Fig. 51. — Ohio Small Ni- trous Oxid Inhaler. May be easily carried to bedside or hospital ward; very satisfactory for short an- esthesia. 160 ANESTHESIA in fixed percentage. If turned still farther, the nitrons oxid is closed off and pure oxygen is administered. If the patient is a deep breather, the gas can be given with in- creased force by simply turning a regulating device on top of the nitrous' oxid and oxygen automatic valves. These are close to the one Fig. 52. — Connell,'s Anesthbtometer. valve referred to, and are so easy to operate that there is no danger of confusion. The monovalve is made in two designs, one especially for offices and hospitals, where it is easily moved about on castors, and another design, which can be packed up and carried around from place to place. Boothby and Cotton Apparatus. — The apparatus of Boothby and Cotton seems to mark a distinct step in advance. The apparatus is not portable, but is especially applicable for hospital use. NITROUS OXID 161 a perfected apparatus' with notes on administration => "Desirability of Constant Mixture and Necessity of Ether Addition. — All experimental and clinical worlv lias emphasized the fact that a constant mixture (rightly proportioned for the particular case in hand) produces a smoother anesthesia than a mixture of vary- ing composition; in other words, it has been shown that an intermit- tent and irregular supply of either gas does not conduce to a smooth surgical an- esthesia. "Hewitt was the first to develop an ap- paratus at all applicable for general surgi- cal use. His methods of overcoming the pressures of the nitrous oxid and oxygen in the tanks is to use semi-elastic bags which are kept more or less full from the tanks by means of an intermittent flow of the gases controlled directly by hand valves. From these bags the flow of gas to the patient is regulated by a specially constructed and graduated valve that al- lows definite proportions of gas to pass from each bag, providing the pressures within the same are equal. "In practice it has been found very difficult to keep the two bags evenly and equally distended, even if great pains and constant attention are being given by the operator to the manipulation of the hand valves; therefore, the pressure in the two bags varies and, consequently, the mix- ture actually received by the patient must of necessity be very varied. "Fundamental Principles. In- volved IN Securing Constant Mix- tures. — As a result of the inadequacy of any apparatus built on the principle of the Hewitt, we took up, now over a year ago, the study of the problem. We laid down four fundamental principles which were to be met, namely: ^See Figs. 54-55. * Written by Frederic J. Cotton, First Assistant Surgeon, Boston City Hos- pital, and Walter M. Boothby, Assistant in Anatomy, Har^-ard Medical School, Assistant Surgeon, Mount Sinai Hospital (Boston, Mass.), Anesthetist to the Boston City Hospital, Fig. 53. — Pressure Gauges for Large Tanks of Nitrous Oxid and Oxygen. 162 ANESTHESIA "(1) There must be an absolutely regular flow of each gas at any rate desired, without the necessity of frequent valve manipulation. "(2) The flow of the gases must be rendered visible so that their proportions can be approximately estimated at a glance. "(3) Kn efficient method of adding ether vapor gradually yet rap- 1C ife-. < 11.4.1 ^ ^s• HHHH =« 0.353 0.334. E < W^^'^y^fi^L PROPOUND £7.03^ &6t r to • t '-' " % -^ OEtP 0.173 o. Esa 1" 2 k^^^ ^^^ ""-^ ' ME.DIUM 4-a,5 z ta* " 15 • o. IB7S o.iAes iiiiiiliiiiii '^ i-iGMT Al.l*^ 4-. II lO • O.I273 <> llo? •i.^f-i""j"%>.?^" Subconscious X i-iSht SuB-conS 6 CONFUSION |5. IZ 1.99 s- oaAiE a.os&3 Fig. IOS.^Chart I, Showing the Necessary Percentage of Ether Vapor for the Endophabyngeal or Endotracheal Administration. patient is conscious, the reflex contraction of the glottis prevents the irrespirable gas or vapors from entering the finest air passages." The anesthetist should take care that the lungs of the narcotized patient are not injured. In a closed inhaler the percentage of carbonic acid met with in these experiments, even with healthy persons, was never high enough to produce the slightest narcosis, "therefore the percentage of carbonic acid met with in the air of the masks could not be looked upon as having a paralyzing or narcotizing effect." Karl Connell ^ was the first to develop the accurate percentages of ether necessary for surgical anesthesia when given by the vapor method either endopharyngeally or endotracheally. These charts represent a composite of three hundred cases of surgical anesthesia at the Eoose- velt Hospital charted after a working experience had been gained on a previous, series of about six hundred cases. Chart I indicates the zones of ether anesthesia in terms of weight ^ Extracts from a paper read by invitation before the first annual meeting of the American Association of Anesthetists, Minn., June 18, 1913. 242 ANESTHESIA of ether to air delivered under working conditions. The volumetric equivalent and ether vapor pressure equivalent are tabulated in parallel columns, as is the absolute weight of ether per liter in the air at de- livery and at body temperature. These zon-es are for practical working guidance in surgical etheriza- tion, and are not absolute. The zones above the 15 per cent level gradu- ally lower toward that level as the anesthetic tension of about 48 milli- ZONCfr OP ANE.6TKv.IA PR.OPOUr-40 euacoNscious ^T SuB -CONS. COI<4Fu.filOM %IMCM. PTiBL4TYPt — •-AUCOHOklc TYPL Fig. 109. — Chart II, Showing the Most Advantageous Ether Pressure. meters of the entire body is attained. At the end of an hour of full anesthesia even the zone of deep anesthesia for a considerable length of time might result lethally. For example, when a dog, after anesthetic saturation, is carried in the zone of profound anesthesia by endotracheal delivery, respiratory effort ceases in about an hour, only to begin again when the ether tension is lowered. Such dosage would result fatally if provision is not made for artificial respiration. These zones are the same whether the delivery be by face-mask or by insufflation. Chart II shows the most advantageous ether pressure to maintain in the pulmonary air, charted in terms of weight of ether in air under usual working conditions at sea level. The percentages above 15 per cent during the preliminary and early stage of full surgical anesthesia are needed to establish the proper anesthetic tension in the arterial blood to the sensorium pending such ETHER 243 time as the entire circulating and fixed tissues oJ; the body are brought to uniform tension. As seen on the chart, there is a difference of 20 to 30 minutes between the length of time such saturation takes in a man of the young, robust, or alcoholic type to the much shorter time taken to saturate the small, relaxed woman or child. All types, how- ever, when the general tension is once established, run on the same base line. This, for complete anesthesia, is between 14 per cent and 15 per cent by weight of ether, yielding a tension between 45 and 51 milli- meters. The absolute point is not as yet fully established, but is proba- bly about 48 millimeters. In fact, it would seem from preliminary ob- servation that this tension is basic not alone for all types of man, but also for the entire animal kingdom. Below this level the operative case may be carried where only light anesthesia is desired, or when the operation reaches such a stage that protection against shock influence is no longer needed (i. e., that very effective protection conferred by full ether anesthesia), or where the anesthetist desires the patient to enter the zone of slow ether desaturation and recovering consciousness. This recovery zone may be so gauged that in short operations the patient leaves the table practically conscious and, even after long operations, in full possession of all pharyngeal reflexes. Saturation of the arterial blood and sensorium is complete in the curve shown, to the extent of full surgical anesthesia, in about two min- utes for each liter of circulating blood, being complete in medium- sized children in six minutes, and in ^ the adult in twelve minutes. Operations, even major procedures, may be begun before full relaxation is established or at the peak of the preliminary curve, say at the end of six minutes in a docile adult. Yet where it is desired to fully pro- tect the patient against shock-producing and inhibitory influences, it is desirable to wait for full surgical relaxation, i. e., about ten to twelve minutes. While the arterial blood to the sensorium may be fully charged by high percentages within ten minutes, yet the general body of an adult is not brought to full tension, approximating 48 millimeters, by the delivery curve shown, for from forty to sixty minutes. Desaturation proceeds even more slowly, although marked changes of deadened or awakened sensibility may be seen within three minutes by increase or decrease of ten millimeters of ether vapor pressure in the air deliv- ered. This, sensitiveness is more pronounced before the anesthetic ten- sion of the entire body is established. Partial recovery is more rapid than deepening anesthesia by changes of equal degree before saturation is complete. After the anesthetic tension is established, anesthesia may be more rapidly deepened than diminished, an observation readily ex- plicable on physical and chemical grounds. The patient may be carried in the zone of profound anesthesia or 244 ANESTHESIA deep, medium, or light anesthesia at will. With the data at present in hand, the most advantageous anesthetization by ether can be plotted in advance for the type of individual and for the nature and stage of the operation, and maintained after the initial stage entirely automatically, and, were it, desirable, without the presence of any anesthetist. The ether intoxication may be reduced to a small factor and shock influence effectively blocked. Conclusions. — The percentages of ether needed by man are well established, and the most advantageous anesthesia may be plotted in advance. These percentages are probably basic for the animal kingdom. Fig. 110. — ^Administration of Warmed Ether Vapor by the Closed Method. A curve plotted for man for advantageous etherization rapidly ascends in the preliminary stage to 30 to 45 per cent by weight of ether in air, after five minutes it falls, reaching 26 per cent by the tenth minute, when surgical relaxation is well established. Through the next half hour it scales downward, reaching 15 per cent in 30 or 40 minutes. It runs on or about this base line for some hours, descending when the zone of recovery is desired to be entered. The Closed Method.— When the closed method is decided upon, any mask and bag used in the gas-ether sequence may be employed. A rubber tube from the three-bottle vapor inhaler in this instance will be attached to the stopcock of the bag. The expiratory valve will be left slightly open so as to have the escape of a small amount of air at all times, while at the same time constant rebreathing is maintained. The inspiratory valve of the inhaler should be out of commission. Air should be constantly forced in, and the bag kept about nine-tenths full so that no effort either to inhale or exhale is exacted of the patient. With vigorous pumping a bead of 1/8 to i/4 of an inch in height will be maintained in the ether bottle. Continuous pumping must be ETHER 245 maintained throughout the administration of the anesthetic. Toward the close of the anesthesia tlie tubes from the pumping apparatus and of the mask should be detached from the three-bottle vapor inhaler and at- tached to the warming apparatus, and the patient's lungs thus thoroughly aerated before the mask is removed from the face, the bag to be tjo inflated as before. This should be done from five to ten minutes before the completion of the operation so that by the time the operation is Fig. 111.— Diagrammatic Sketch of the Nitrous Oxid-Sther Vapor Sequence. finished the patient's reflexes will all be present and he will be practically from under the influence of the anesthetic. Amount of the Anesthetic "Used. — With the closed vapor method usually two (rarely three) ounces of ether per hour are required; if three ounces are used the first hour, one ounce will suffice the second hour. With the open method, three to four ounces of ether are necessary to maintain complete relaxation. Care of the Apparatus. — All the ether and chloroform remaining in the apparatus should be thrown away. The water bottle should be emptied, and the bottles detached from the apparatus (this last pro- cedure in order to save the rubber washers). The mask and bag should be thrown into the sterilizer and boiled as are other surgical apparatuses, or they should be thoroughly rinsed in carbolic 1-40 or bichlorid solu- tion and then rinsed in cold water. If a tube or moiith gag is used, it should also be thoroughly boiled after each operation. Hints. — The principal care of the anesthetist with any vapor appa- 246 ANESTPIESIA ratus is to see that there is no leakage, either at the bottles or face- piece or bag, also that no kinks occur in the rubber tubing or that pres- sure is not made on the tube by assistants or nurses. Advantages. — The following are the advantages of the vapor method : First: The small amount of the anesthetic used, two to four drams for a thirty-minute operation, or two or three ounces of ether per hour. Second: The technique is easily acquired. Third : Objectionable mucous rale is usually entirely absent. Fourth: In over ninety per cent of cases there are no unpleasant after-effects. Fifth : A continuous plane of narcosis is easily maintained. Sixth: An intermitting narcosis which is wrong in principle is avoided. Seventh : The passage back and forth over the dangerous vomiting center is usually made easily. Treatment of Accidents. — When respiration ceases the first thing to do is to give the patient a quick, hard slap upon the chest. If this does not start the respiration, the next movement is to place the hands upon the side walls of the chest and press very hard several times in succes- sion. If the patient does not begin to breathe immediately the follow- ing procedures must be followed and in much quicker time than it takes to give the directions : First: Insert a mouth gag and pull the tongue well forward. Second : Lower the head, and while this is being done pressure upon the side walls of the chest must be continued. As soon as the patient is lowered to the Trendelenburg position, grasp the arms just above the elbows, and press them vigorously to the sides and then draw the arms backward and sideways over the head, at the end of this move- ment making considerable traction. Eepeat this movement about 15 times to the minute. At the same time have an assistant dilate the sphincter ani. Another assistant can be vigorously massaging the pre- cordial region while artificial respiration is being kept up. If there are a sufficient number of nurses or assistants standing around, bandages starting at the feet and continued to the thighs with the idea of ex- pressing the blood in the extremities to the body is sometimes beneficial. If these procedures do not give some definite result within two minutes, the Lewis pendulum swing should be attempted. If respiratory arrest is due to mucus or saliva, the anesthetic must be discontinued, a mouth gag inserted, and the upper air passages swabbed out with a sponge placed upon a long sponge holder. If the fourth stage is brought on by hemorrhage or shock from handling important nerves or blood vessels, and the respiration is still good and a dilute ether vapor has been given, a Trendelenburg position with bandaging of the lower limbs and intravenous saline infusion will ETHER 247 usually rectify this condition. If the fourth stage is anticipated from certain events, it may be sometimes prevented by a hot rectal saline infusion. It is not unusual where the patient is in an extreme condi- tion to start a hypodermoclysis at the time the operation is commenced. According to American statistics, one death occurs in 5,623 adminis- trations of ether by the drop or vapor method. This means that death is due to gross carelessness or ignorance. In extremely rare and unusual cases of status lymphaticus, in which the organs may be diseased and anomalous, such as a very small heart with a large aorta and enlargement of the tongue, it is quite con- ceivable that the heart may be paralyzed before the respiration ceases. When paralysis occurs from this condition it is usually during primary anesthesia. If the anesthesia is continued for 15 minutes or over, compensation occurs and a death after that time could hardly be at- tributed to this cause. INDICATIONS AND CONTRAINDICATIONS OF ETHER Indications. — Hewitt states that in "healthy and moderately healthy subjects the risk connected with the administration of ether is very slight, the reported fatalities having almost invariably taken place in exhausted or markedly diseased individuals." The senior author agrees with Hewitt as to the risk connected with the administration of ether. With the modern methods of administration, and with the combina- tions and sequences which make it possible to adapt the anesthetic to the patient, the indications for ether almost parallel the indications for operation, except, of course, for very short surgical interventions. Ethe.' is especially indicated to continue the narcosis in operations about the mouth or nose, such as excision of the tongue or lower jaw, where there is considerable shock. Ether by the vapor or drop method is indicated for adenoid and tonsil cases, and wherever the status lymphaticus is suspected. Wher- ever a deep anesthesia is desired, ether by the closed method is indi- cated, as for amputations, dislocations, genito-urinary operations, lapa- rotomies, excision of the breast, amputation of the cervix, vaginal and supravaginal hysterectomy, and in all conditions of shock and collapse. Contraindications. — The first objection to any method of adminis- tration of ether is where the patient has suffered intensely from a pre- vious administration of this drug, and expresses a decided dislike for the odor and after-effects. Such idiosyncrasies must be respected. The senior author knows of one death caused by disregarding this rule. The history of this case is appended. 248 ANESTHESIA Patient, female, aged 35 years. Operation, removal of ovarian tumor. The anesthetist was warned not to use ether, as nausea and vomiting of an exaggerated type had followed a previous administra- tion of this agent. The anesthesia was begun with chloroform, but as surgical anesthesia was reached pulse, respiration, and color seemed to indicate a change. A few drops of ether were placed upon the mask to stimulate the patient. Almost immediately vomiting ensued. Upon deepening the anesthesia vomiting ceased, and a smooth narcosis en- sued to the end of the operation. Ether was used from time to time as needed. As the patient came out of the anesthetic vomiting started again, and continued, with intermissions, for forty-eight hours. The character of this vomiting was so violent that a retention stitch was broken and a small piece of intestine was caught in the wound. When the dressings were removed the tissues along the line of incision ap- peared tense and swollen. Upon reopening the wound, the gut was found to be gangrenous, and this portion was removed under an anes- thetic. In spite of good nursing, peritonitis and death followed. Nitrous oxid and oxygen would probably have saved the life of this patient. Kocher ^ states that respiratory disturbances and pathological changes in the respiratory organs, with dyspnea, are contraindications of prime importance. Ether, he holds, causes more suffering and more lasting damage to the respiratory organs than can be attributed to chloroform. In lung and kidney disease, bronchitis, phthisis, dyspnea, and em- physema, and in ophthalmic operations, patients do better with some other anesthetic than ether. In aneurism and atheroma ether is contraindicated. It is also contraindicated in acute attacks of asthma or bronchitis. In chronic bronchitis or asthma ether introduced cautiously and given by modern methods is perfectly safe. In any condition with high blood pressure ether is contraindicated. Mortimer ^ states that ether should not, as a rule, be given to in- fants and young children, in whom it excites much mucous secretion which may embarrass breathing or lead to bronchitis. Elderly people do not usually take ether well, because of the de- generate state of the respiratory and circulatory systems. Heavy smok- ers and people whose mouths and throats are in an unhealthy state, who are likely to cough and secrete much mucus and to have enlarge- ment of the tongue and upper air passages, are considered by Mortimer ^ as unfavorable subjects for ether. ^ ' ' Text-Book of Operative Surgery, ' ' 50. ^ ' ' Anesthesia and Analgesia, ' ' 55. ^ Loc. cit. ETHER 249 Ether is contraindicated if an actual cautery, a lamp, or any kind of electrical spark is to be employed. Most writers state that ether is contraindicated in operations upon the brain, because of the desirability of having the field of operation as free from blood as possible. Many surgeons, however, prefer the drop, or vapor, method of ether in all operations upon the brain. Similarly, exophthalmic goiter is stated as contraindicated, but many surgeons pre- fer ether by the open method for this operation. CHAPTER VI ETHYL CHLOEID Chemistry : Chemical History ; History of Its Use as an Anesthetic ; Uses; Preparation; Properties; Storage and Containers; Impurities Which May Develop in Ethyl Chlorid ; Detection of Impurities in Ethyl Chlorid. Physiology : Effects upon Eespiratory System ; Effects upon the Circulatory System ; Effects upon the IsTervous System ; Effects upon the Muscular System ; Effects upon the Glandular System ; Causes of Death under Ethyl Chlorid Anesthesia; Stages of Anesthesia; Elimination; Af ter-Effects ; Comparison with Other Anesthetic Agents. Indications and Contraindications. Administration: Experimental Data; Methods of Administration; Open Method; Semi-closed Method; Closed Method; Combinations and Sequences. Bibliography. CHEMISTRY Chemical History. — Ethyl chlorid ("sweet spirit of salt"; cetJiylum chloratum; cether chloratus; cether hydro chloricus seu muriaticus; hydro- chloric ether; chloro-ethane ; monochlorethane ; chlorcethyl ; leichter salzather; ether chlorhydrique; chelen or chelene; kelen or kelene; ano- djmone; antidolorin; ethylol; loco-dolor, etc.) was first obtained in alco- holic solution by Basil Valentine (pseudo-).^ Sweet spirit of salt was ^ He described its preparation thus (DiederJiolung des grossen Steins der uralten Weisen, ed. Petrseus, p. 72 ) : " This I also say that when the spirit of common salt unites with spirit of wine, and Is distilled three times, it be- comes sweet and loses its sharpness." In his "Last Testament" (Basilius Val- entinus, ed. Petrseus, p. 786) he also says: "Take of good spirit of salt which has been well dephlegmated and contains no watery particles one part; pour to this half a part of the best and most concentrated spiritus vini, which also con- tains no phlegma or vegetable mercury. ' ' Valentinus goes on to state that this mixture must be repeatedly distilled, and then "placed in a well-closed bottle and allowed to stand for a month or until it has all become quite sweet and has lost its acid taste. Thus is the spiritus salis et vini prepared, and may be readily extracted. ' ' In 1739 Johann Pott demonstrated that sweet spirit of salt could be ob- 250 ETHYL CHLORID 251 well known to the later chemists. Glauber, for example, referred to it in 1648. In 1749 ^ Ludollf stated that, on heating ah^ohol with sulphuric acid and sodium chlorid, a distillate was obtained whi(;h, when treated with lime, yielded an ether, but he endeavored in vain to obtain a sim- ilar compound by the action of hydrogen chlorid (muriatic gas) on alcohol. Baume was also unsuccessful in this direction, but Woulfe ^ obtained the preparation in this way, and it was afterwards prepared and sold by an apothecary in Germany under the name of "Basse's hydrochloric ether'' (1801). History of Its "Use as an Anesthetic. — Flourens ^ drew attention to the anesthetic properties of ethyl chlorid in 1847, and Heyf elder, in the following year, first administered the vapor for surgical purposes. ■Unsatisfactory symptoms often accompanied its administration at that time, these effects being attributed to imperfection in the manufacture and the consequent presence of impurities. The use of the agent as a general anesthetic was abandoned until 1895, since which time it has rapidly gained in favor. This is principally attributable to the improved methods of administration and to an increase in the knowledge of its properties and physiological action; and last, but not least, to improve- ments in its manufacture. Ethyl chlorid may be regarded as ethyl alcohol (CHgCHgOH), in which the OH has been replaced by CI; hence the formula CH3CH2CI, which was established by Colin and Robiquet.* Alcoholic muriatic ether is a solution of ethyl chlorid in an equal amount of alcohol by volume. It has been used as an internal stimulant in doses of 0.6 to 1.8 c.c. Uses. — So far ethyl chlorid has not been used technically, although Palmer ° called attention to its advantages (and disadvantages) as an industrial refrigerating agent. In medicine it is used for (a) general anesthesia (by inhalation) ; (b) local anesthesia (by external applica- tion, in effect, refrigeration) ; (c) diagnostic and therapeutic purposes. Its physiological action will be referred to later. Preparation. — As noted, ethyl chlorid may be regarded as ethyl alcohol (C2H5OH) in which the hydroxyl has been replaced by chlorin. tained by the action of butter of arsenic or butter of antimony (arsenic or antimony trichlorid) on spirit of wine, and other chemists found that other metallic chlorids might be employed for the same purpose. Eouelle, in 1759, found that ethyl chlorid results from the action of sulphur chlorid, phosphorus pentachlorid, aluminum chlorid, ferric chlorid, stannic chlorid, etc., on alcohol. ^ Die in der Medicin siegende Chemie . . . , Erfurt, 1746-9. ^Phil. Trans., 1767, 520. =* Hewitt: " Anssthetics, " 1907, 11. * Ann. cJiim. phys. (2), 1, 343. ^Eng. Digest, 5, 262. 252 ANESTHESIA Ethyl alcohol is the raw product from which it is usually made, although ethyl chlorid results in the regulated chlorination of ethane/ and on treating acetic and other ethers with hydrogen chlorid by the action of hydrochloric acid on ether in sealed tubes/ and by the action of chlorin on ethyl iodid. In actual practice ethyl alcohol is mixed with hydrogen chlorid, which acts as a desiccating agent itself,^ or dehydrating agents, as zinc chlorid * or phosphorus pentoxid ° are added to remove the water produced. If these agents were not added the reversible reaction would reach an equilibrium. This equilibrium may be avoided by increase of pressure.*^ Impurities from Materials Used. — If pure hydrogen chlorid be used there is little danger of impurities being introduced from that source. The quality of the alcohol used, however, is very important. If denatured alcohol, especially if wood alcohol be the denaturant, or one of the denaturing substances, then methyl chlorid will likely be pro- ^ Darling: Ann., 150, 216; Schorlemmer : Compt. rend., 58, 703. =* Berthelot. ^ Ethyl chlorid may be prepared by distilling ethyl alcohol (5 parts), sul- phuric acid (2 parts), and sodium chlorid (12 parts) together, or by passing dry hydrogen chlorid into absolute alcohol; but it is said that the action of hydrochloric acid upon alcohol gives a poor yield of chlorid unless zinc chlo- rid is added to the alcohol before passing in hydrochloric acid (Groves: J. Chem. Soc, 1874, S7, 637). Groves found that when hydrochloric acid gas was passed into a boiling solution of zinc chlorid (2 parts) in 95 per cent ethyl alcohol (3 parts), the yield was nearly theoretical. He purified the product by wash- ing with water. *Kruger [J. prakt. Chem. (2) 14, 193] recommended that a mixture of one part of zinc chlorid in 82 parts of ethyl alcohol should be saturated with hydro- chloric acid gas in the cold, and then heated to the boiling point. Hydrochloric acid gas being conducted into the mixture during distillation, as the process is carried out, a reflux condenser prevents the alcohol vapor from coming over, and the zinc chlorid is said to act by abstracting water from the alcohol, the nascent ethylene combining with hydrogen chlorid to form ethyl chlorid, according to Schorlemmer (/. Chem. Soc., 1876, 308). On the action of hydrochloric acid on alcohol, alone and in the presence of zinc chlorid, see also Robiquet and Colin: Ann. chim. phys. (2), 1, 343; Regnault, ibid. (2) 71, 355; Kuhlmann: Ann., S3, 108; and Lowig, Pogg.: Ann., 45, 346. On velocity of the reaction, see Kailan: Monatsh., 1907, 28, 559. The formation of ethyl chlorid in this process is partly due to the action of hydrogen chlorid upon alcohol, and partly to the union of this nascent ethylene with hydrogen chlorid. ° The practice of some American manufacturers is to use phosphorus pen- toxid as the dehydrating agent. * The process of Mennet and Cartier (French Patent, 206, 574, June 23, 1890) relates to the production of ethyl chlorid. An autoclave of 150 liters capacity as used, into which a mixture of 95 kg. of hydrochloric acid (21° Be.) and 34 kg. of 93-95 per cent ethyl alcohol is maintained at 50 atmospheres pressure and at 130° C. for about 28 hours. The pressure is then diminished to 42 atmospheres, and finally the autoclave is cooled. See also Hager's Handhuch d. pharm. Praxis, 1910, 1, 189. ETHYL CHLORID 253 duced. This gas (b.p., — 24° C), while very soluble in ethyl cfilorid, may easily be removed by rectification. Aldehyds form compounds with hydrogen chlorid. Any acetic acid present is liable to form acetyl chlorid, and the higher alcohols, as propyl, butyl and amyl, produce their corresponding halogen derivatives. It is desirable, therefore, to use only absolute alcohol of the highest degree of rectification. An examination of seven different makes of ethyl chlorid obtainable in London in 1905 showed that all the branded samples were pure, as was also one unbranded sample. The report of this investigation ^ states that ethyl chlorid should be free from water, foreign chlorids, acids, aldehyds, ether, alcohol, and organo-metallic substances. Purification. — Ethyl chlorid is purified - by passing the vapor through water, dilute caustic solution, and then concentrated sulphuric acid. This treatment is intended to free it from alcohol,^ hydrogen chlorid,* and water. Redistillation is sometimes practiced. This rec- tification serves to remove other alkyl chlorids, the methyl going off in the first fractions of the distillate, and the higher compounds remain- ing in the residue. Properties. — Ethyl chlorid is a colorless mobile liquid at low tem- peratures and is exceedingly volatile. It possesses a sweetish taste and a pungent, yet fragrant, "ethereal" odor. It is inflammable, burning, when ignited, with a smoky green-edged flame, producing fumes of hydrogen chlorid; hence care must be exercised in using it near an open flame or a hot cautery. It even decomposes when very close to a hot bulb or an incandescent electric light. Ethyl chlorid does not freeze at — 29° C; it possesses a boiling point of +12.5° C.^; and its specific gravity is 0.92138 at 0° % 0.9176 at +8° \ 0.9510 at +12° «, and at +25° ^ the vapor has a specific gi'avity of 0.91708. Its vapor density is 2.22. Water dissolves about one-fiftieth of its weight of ethyl chlorid and acquires a sweetish, ethereal taste. Ethyl chlorid is readily soluble in ethyl alcohol and ethyl ether, and neither solution should give a reaction with silver nitrate solution, as ethyl chlorid itself does not react with silver nitrate at ordinary temperatures. Ethyl chlorid dissolves phos- phorus, sulphur, fats, oils, and many resins. It combines with many "■Lancet, 1905, ii, 1631. 'Pharm. J. (4), 15, 694. "Acetyl chlorid decomposes to acetic and hydrochloric acids with water. * And other bodies forming acids with water. = Regnault: Jahresber., 1863, 67. "Pierre: Coiwpt. rend., 27, 213. Darling {Jahresber., 21, 328) found a density of 0.9252 at this temperature. ^Linnemann: Ann., 160, 195. ' Ramsay : J. Chem. Soc., 35, 470. 'Perkin: J. prakt. Chem. (2), 31, 481. 254 ANESTHESIA metallic chlorids — for example, antimony pentachlorid and ferric chlorid — to form crystalline compounds. Storage and Containers. — Owing to its extreme volatility, ethyl chlorid. cannot be kept in ordinary bottles, excej^t at a temperature be- FiG. 112. — Sealed Tubes of Ethyl Chlorid. These contain 3 and 5 c.c. for use in various inhalers for general anesthesia. *i,->.'-\^'--.v^ Fig. 113. — Double-End Ethyl Chlorid Tube. This possesses the advantage of enabling the operator to utilize the spray whose emerging angle will be most conven- ient. They are put up in 10 and 30 gm sizes. Fig. 114. — Automatic Closing Tube for Ethyl Chlorid. These are made to hold 10, 30, and 60 gm of ethyl chlorid and are used for local and general anesthesia. They may be graduated. The tube is glass, but the automatic cap is made of a non- corroding metal. Fig. 115. — Automatic Closing Tube for Ethyl Chlorid. It is graduated in cubic centimeters for discharging any desired amount and containing 60 c.c. Fig. 116. — Flexible Spraying Nozzle. This is detachable, made of soft German silver tubing, and enables the operator to reach any tooth and to enter the nose, throat or external auditory canal to apply ethyl chlorid as a local anesthetic. low -+-10° C, and even then the stopper must be tight-fitting and very well secured, and the bottles should preferably be stored in an inverted position. Ethyl chlorid is now supplied on the market in sealed or mechanically capped glass or metal tubes of convenient forms, wherein the ethyl chlorid is held under pressure. Automatic closing tubes are ETHYL CHLORID 255 preferable for local anesthesia, and there are at least five different types of these on the American market, each manufacturer using his special form of container, some of which arc described here. Ethyl chlorid is also furnished by certain manufacturers in plain capped tubes. Containers of ethyl chlorid should be kept in a dark, cool place, re- mote from lights or fire; and no empty tiibes should be refilled with a nBi.JI,jHi,'J, J" -,ll«liU»!l.|!!!!l!!»lll!IIIW-%u' 50 p.c. Fig. 117. — Ferguson's Ethyl Chlorid Tubes for General and Local Anesthesia. A. — 50 c.c. tube of ethyl chlorid intended for general anesthesia only. The capillary is gauged so as to deliver the proper amount of ethyl chlorid in the right time to produce a satisfactory narcosis. It is graduated and has a large capillary bore. It is not adapted for producing local anesthesia. B. — 50 c.c. tube open, showing the graduations. C. — Tubes containing respectively 30 c.c. or 60 c.c. of ethyl chlorid are made for local anesthesia only. The capillary on each is of the same size, and is gauged so as to deliver the minimum amount of ethyl chlorid compatible with a good local anesthesia, thereby preventing waste. These tubes differ from the 50 c.c. tube in capacity and size of capillary bore, and are not adapted for producing general anesthesia except in the case of infants or young children, and very susceptible subjects. Open the tube by pushing the thumb button forward as far as it will go in a direction parallel with the long axis of the tube. Do not press down on the button, as by doing so the capillary tube may be broken. When through using, remove the thumb from the button and allow the spring to bring the cap back in place; the tube is thus closed instantaneously and tightly. If any foreign matter becomes lodged on the end of the capillary tube, interfering with its free working, gently wipe it off with the finger, at the same time grasping the tube in the hand to cause pressure by body heat and to drive the obstructing particles out. Never try to free it with a needle, pin or other instrument. fresh lot of the compound, since such an economy may result in spread- ing infection. Glass as Compared ivith Metal Containers. — It is maintained by some that ethyl chlorid decomposes when exposed to air and sunlight; hence that the drug should be kept in metal containers. It is further claimed that, inasmuch as ethyl chlorid is inflammable, there is less danger of breaking in accidentally dropping the metal container. In opposition to this, it may be said that, in filling any container, no air remains in it on account of the great volatility of ethyl chlorid. Furthermore, in draw- ing off a' portion of the contents of a tube, pressure is produced within the tube which is constant for each temperature, it matters not how much liquid ethyl chlorid is present, so long as there is some liquid 256 ANESTHESIA there ; hence no backward pressure is created, whereby air may be sucked into the tube. Undoubtedly light facilitates the decomposition of ethyl Fia. 118. — The Gebauer Container for Ethyl Chlorid. chlorid by oxygen, but it has not been shown that light produces any change in ethyl chlorid when oxygen is absent. Assuming that the ethyl chlorid is pure, there is another objection to the use of a metal Fig. 119. — Technic of Ethyl Chlorid Measure-Dropper. Attach the measure-drop- per to an ethyl chlorid tube; holding the tube in a horizontal position with the apex of the dropper pointing down, open the valve in the tube by gradually turning the screw to the right, allowing the ethyl chlorid to fill the chamber in the dropper, at the same time holding the thumb over the opening in the apex of the dropper as shown in cut. When the graduated chamber in the dropper is filled to the desired amount, close valve again. Now hold the tube with the apex of the dropper pointing downward about two or three inches directly above the gauze in the inhaler and remove the thumb. The ethyl chlorid will now issue from the dropper in forms of drops, which are directed upon the gauze in the inhaler. As a general rule 3 to 5 c.c. will suffice to anesthetize a person for a short operation, but there is no fixed rule as to the quantity of ethyl chlorid required, since some will take more than others. The anesthetist must be guided entirely by the symptoms of his patient as to the duration and quantity of the ethyl chlorid required. If it is observed that 3 c.c. will not suffice to anesthetize the patient, one simply opens the valve again in the tube and lets 1 or 2 c.c. more of ethyl chlorid flow into the gradu- ated chamber of the dropper and proceeds as before. If the ethyl chlorid does not drop fast enough from the apex of the dropper, it can be made to drop faster by placing the thumb or finger over the opening in the neck of the dropper marked "A". With a little practice the dropping may be regulated. container, namely, inability to tell how much of the preparation is within the tube and how much has been or is being used in the anesthesia. This has been met by having a graduated (3 c.c. capacity) dropper made of glass, which may be attached to the metal container. The design of such a dropper is shown in Figure 119. ETHYL CHLORID 257 Impurities Which May Develop in Ethyl Chlorid. — Uncertain re- sults have been encountered by several vi^ho have used ethyl chlorid for general anesthesia and these have been attributed in some cases to im- purities that were present and were later detected chemically.^ The original product must not have been properly purified, for the conditions essential for the decomposition of ethyl chlorid itself in- volve oxygen, and, as animadverted, oxygen has no opportunity to enter the receptacle in which ethyl chlorid is dispensed. The presence of small amounts of water may bring about a reverse change in ethyl chlorid, with the formation of ethyl alcohol and hydrogen chlorid. The latter may readily be detected by spraying some of the drug into a clear silver nitrate solution. The appearance of a turbidity indicates free hydrogen chlorid, as pure ethyl chlorid does not thus react with silver nitrate. Detection of Impurities in Ethyl Chlorid. — The impurities likely to occur in ethyl chlorid are (a) those which it brings with it from the manufacturer and (b) those resulting through careless storage. While the exact nature of all of these is unknown, yet ethyl chlorid, complying with the requirements of the pharmacopoeias as given below, is entirely suitable for the purjDoses for which it is intended. On account of its volatility, the examination of ethyl chlorid presents more difficulties than are encountered in the cases of ethyl ether and chloroform; and it is indeed fortunate that it may be easily prepared in a state of com- parative chemical purity. The Pharmaeopceia of the United States ^ prescribes the following tests for purity : 1. "If 10 c.c. of ethyl chlorid, while cold, be dissolved in alcohol, and a few drops of silver nitrate T. S. be added, no turbidity should be produced (absence of liydrocldoric acid). 2. "If 10 c.c. of ethyl chlorid be agitated with 10 c.c. of cold water and the supernatant stratum of ethyl chlorid be evaporated spontane- ously, and if a few drops of potassium dichromate T. S. be added to the remaining aqueous liquid, followed by some diluted sulphuric acid, and the mixture be boiled, no odor of aldehyd should be developed, and a greenish or purplish color should not be produced in the liquid {absence of alcohol). 3. "On allowing ethyl chlorid to evaporate from clean, odorless blotting paper, which has been saturated with it, no unpleasant odor should remain upon the paper (absence of sulphur compounds, etc.)." The British Pharmacopaiia requires that it should leave no residue on evaporation and that an aqueous or alcohol extract should have no acid reaction with blue litmus paper. The Deutsches Arzneibuch ^ requires ^Hawley: J. Am. Med. Assn., 1906, 47, 502. ^ 8th decennial revision, 32. 2 1910, 37. 258 ANESTHESIA also that "during evaporation, and, thereafter, no garlic odor should be apparent (phosphorus compounds)." The French Codex, ^ while giving the incorrect specific gravity, states it should be free from ethyl bromid and iodid. The Pharmacopoeia Helvetica ^ requires that, when its vapors are led through water, the water must not give an acid reaction with litmus nor a reaction with silver nitrate. All the tests seek to eliminate acids. PHYSIOLOGY One of us (J. T. G.) has not employed ethyl chlorid, either in the laboratory or in the operating room, to such an extent as to warrant the consideration of this agent from the point of view of personal experience. In the pages which follow, therefore, the reported work of other investi- gators is freely and almost exclusively utilized. Effects Upon the Respiratory System. — The effect of ethyl chlorid upon the lungs, according to Miiller,^ is pathological rather than physio- logical. Cole * found that, when given in the form commercially known as somnoform (see p. 818), ethyl chlorid markedly increased the size and rate of contraction and the tone of the diaphragm, which remained in a state of strong tonic contraction, the heart still beating strongly. Embley ^ found, from his experiments upon animals, that, as the blood pressure fell, respiration ceased, and, as the blood pressure rose, the respiration returned. He does not, therefore, agree with other in- vestigators in the view that respiration may be paralyzed by ethyl chlorid independently of fall of blood pressure, in ordinary administra- »1908, 249. =* 1907, 27. ^Miiller, B.: " Narkologie, " 1, 454. *Cole: Proc. Physiol. Soc, June lb, 1903; J. Physiol, 29, 25. ^Embley: Proc. Roy. Soc, 78, 31 (1906); Pharm. J. (4), 24, 650; Lancet, April 20, 1907. The solubility of ethyl chlorid vapor in water at normal pres- sure and +21° C. is 253.36 per cent by volume (0.678 per cent by weight) ; and the solubility in blood is approximately 500 per cent of vapor by volume at 38° C. The heart muscle is paralyzed by ethyl chlorid just as it is by chloroform and in contrast with ethyl ether, but the quantity of ethyl chlorid vapor in air required is nineteen times as great as that of chloroform to produce similar results. On the vascular system the net result is dilatation, but the degree of paralysis is strikingly less than that produced by chloroform, even when the latter is present in less than one-tenth of the quantity of air inspired. A strength of 5 to 7 per cent of ethyl chlorid vapor in the air required appears to be the limit of safety from danger of syncope in dogs for prolonged and continuous administration, and the conclusions arrived at by Embley are con- sidered to apply to man. For the administration of ethyl chlorid he advises employing a gasometer containing the proper mixture of air and ethyl chlorid vapor. ETHYL CHLORID 259 tions. Eespiratory arrest is preceded by a remarkable prolongation of the respiratory pause. In none of Embley's experiments was the heart arrested before respiration. The integrity of the respiratory mechanism in ethyl chlorid narcosis, he holds, is dependent upon the maintenance of blood pressure. Eespiratory frequency is not affected as a rule ; but McCardie ^ states that ethyl chlorid quickens and deepens respiration. Effects Upon the Circulatory System. — According to Miiller," the solubility of ethyl chlorid in water is slight and the solution very loose, for which reasons the blood-serum takes up only a slight amount. It is not much more soluble in blood-serum than in pure water. A small amount is, however, taken up by the blood corpuscles. On account of its slight solubility in blood-serum, very highly concentrated mixtures of air and ethyl chlorid must be carried to the lungs, for, in consequence of the loose solution, the vapor is at once given off from the blood, the patient awakening promptly unless such highly concentrated mixtures are administered. Embley,^ who investigated the pharmacology of ethyl chlorid, found that the solubility of the vapor in water at normal pressure and 21° C. is 253°, 36 per cent by volume (0.G78 per cent by weight) ; and the solu- bility in blood is approximately 500 per cent of vapor by volume at 38° C. Camus and Nicloux * found that ethyl chlorid is taken up by the blood with great rapidity, and that it is also eliminated very rapidly. All authorities are agreed that in full surgical narcosis with ethyl chlorid a very great fall in blood pressure is noted. Even when given for a short time, according to McCardie,*^ a fall of blood pressure takes place. Embley ^ says : "The effect of ethyl chlorid upon the heart muscle, as is the case with chloroform, is paralytic, but the quantity of ethyl chlorid vapor required in the air is nineteen times as great as that of chloroform to produce comparable results." He further states that the effect of ethyl chlorid upon the arterioles isolated from the central ner- vous system is relaxation. (In this respect also it is similar to chloro- form, but the amount required is vastly greater.) The effects upon the vasomotor mechanism also are parallel with the action of chloroform. From his experimental work Embley found that the action of ethyl ^ McCardie : ' ' The Position of and Mortality from Ethyl Chloride as a General Anesthetic," Brit. Med. J., March 17, 1906, 616. ^ Miiller : Loc. cit. * Embley: Proc. Boy. Soc, 78, 31 (1906) ; Lancet, April 20, 1907; Pliarm. J., 24, 650. * Camus and Nicloux: Compt. rend., 145, 1437. "McCardie: Lancet, Oct. 7, 1905; Brit. Med. J., March 17, 1906. * Embley : Loc. cit. 260 ANESTHESIA chlorid on the vascular system caused dilatation. The degree of paraly- sis, however, is strikingly less than that produced by chloroform, "even when the latter is present in less than 1/10 of the quantity of the air inspired.'^ Embley concludes: (1) That vagus inhibition of the heart occurs very readily in ethyl chlorid vapor of a strength of ten per cent and upward when administered in the air inspired; (2) that sudden fall of blood pressure occurred during the administration of ethyl chlorid vapor in a strength ranging from ten to twenty per cent, owing to vagus in- hibition of the heart. If thirty per cent is administered, fall of blood pressure is due to weakening of the cardiac arterial musculature; (3) that cardiac inhibition is not so serious from ethyl chlorid as it is from chloroform. It requires nineteen times more ethyl chlorid to produce a given degree of cardiac depression than is required of chloroform, while it requires only four times as much to produce cardiac arrest by vagus stimulation; hence, inhibition sets in relatively more rapidly. Herein rests the relative safety of ethyl chlorid. Webster,^ who experimented upon animals with ethyl chlorid, ethyl bromid, and ethyl iodid, says: "The difference of any action between the chlorid, bromid, iodid and somnoform is one of degree only and this degree seems to depend upon the volatility of the drugs." With small doses he found that there was a slight rise in blood pressure, fol- lowed by a return to normal, whereas, with larger doses, the pressure rapidly fell. Buxton ^ states that flushing of the face, due to dilatation of the peripheral vessels, is always associated with ethyl chlorid inhalation, and may account, in part, for any fall of blood pressure that takes place. When large doses of ethyl chlorid are employed the circulatory changes are secondary to the respiratory changes. Eifects "Upon the Nervous System. — Mliller holds that the blood car- ries the gas into the cerebrum and to the ganglion cells, into the fluids of which the ethyl chlorid passes, and is taken up by the cholesterin- lecithin mixtures. This results in paralysis of the cells. But, as the solubility in the cell-juice is slight, only a small amount of ethyl chlorid enters into the cell, insufficient, in short narcosis, to paralyze all the cells. Although the centers of pain-sensation may be paralyzed, the quantities do not always suffice to paralyze the more resistant centers against narcotic agents ; as a result, the reflexes, the muscles, and so forth are not completely paralyzed, inhibited, or relaxed in the anesthesia. It is only after the ethyl chlorid vapors have been inhaled for some time that larger amounts of these vapors collect in the central elements of the ganglion-cells, in the cholesterin-lecithin mixtures (which dissolve larger ^Webster: Bio-Chem. J., 1, 328 (1906). 2 Buxton: "Anaesthetics," 256. ETHYL CHLORID 261 quantities of ethyl chlorid than water or blood-scrum), inducing a total paralysis of the centers. The action upon the nerve tissue was studied by Cantelupc, who found that ethyl chlorid exerted a double action; on tlie one hand a direct chemical action, and on the other an indirect action, due to cere- bral anemia through paralysis of the vasomotor center. The fibers of the white substance, in the cerebrum as well as the cerebellum, are found to present slight degenerative changes, which are interpreted as the ex- pression of the nutritive changes of the nerve-cell, and therefore also of its nervous process, and which still persist at the period of awakening. Such changes may be purely functional, and therefore curable. Effects "Upon the Muscular System. — Muscular rigidity may be pres- ent during the stage of excitement. In some cases, according to Hewitt,^ muscular relaxation accompanies stertor, but there is more often some rigidity. This rigidity in some subjects may be so general as to cul- minate in opisthotonos. The strong tendency to contraction of the masseter muscles has been noted by all administrators of this ethyl chlorid. Effects Upon the Glandular System. — It is held by various observers that the gastric and intestinal functions are slightly influenced ; the secre- tions of the liver and the kidneys are diminished. Causes of Death Tinder Ethyl Chlorid Anesthesia. — From the fore- going discussion of the effects of ethyl chlorid upon the organism we may agree with the statement of Hewitt ^ that ethyl chlorid may prove fatal in two distinct ways, viz.: (1) by simple overdose, ethyl chlorid toxemia, or ethyl chlorid syncope; (2) by intercurrent respiratory em- harrassment (asphyxia). The prominent features of simple overdose, as noted by Hewitt, are : pallor, pulselessness, arrest of breathing, wide dilatation of the pupils, general muscular flaccidity and separation of the lids. Cardiac arrest quickly follows. In death from asphyxia with ethyl chlorid the intercurrent respira- tory embarrassment, according to Hewitt, may depress a circulation al- ready depressed by the agent. The prominent features in this instance are: spasm about the jaws, mouth, tongue, larynx, or respiratory mus- cles. Eespiratory arrest, with some cyanosis, supervenes, followed by cardiac arrest. (For the mortality of ethyl chlorid, see Appendix on Statistics.) Stages of Anesthesia. — The stages of ethyl chlorid anesthesia are a little different from those of the other pulmonary anesthetics. The first stage is an analgesic stage which commences after two or three breaths of the anesthetic, and which lasts over thirty seconds. ^Hewitt: "Anaesthetics," 439. UUd., 455. 262 ANESTHESIA This is the stage before stertor and other signs of anesthesia appear. It is sufficient for opening an abscess, but the operator is taking the risk of causing pain unless he works rapidly. The second stage is a true anesthetic stage which lasts from one to three minutes after removing the mask from the face. In fact, the anesthetic stage is sometimes deepened after the removal of the mask, owing to the absorption of the ethyl chlorid from the lower air passages. On account of the spasm of the masseter, as frequently happens during this stage, it is necessary that a dental prop be inserted between the teeth in all cases, and not only when intra-oral operation is contem- plated. ^ The third stage is again one of analgesia. It lasts from 30 to 40 seconds, during which no sensation is felt, but the patient may talk or move slightly. Just before the patient becomes conscious, swallowing occurs for some little time. The first sense to return is hearing, and the next is sight. The fourth stage, when the administration is continued too far, corresponds to that of other inhalation anesthetics under the same cir- cumstances, viz., the bulb is affected, causing cessation of respiration, arrest of the heart, and death. In prolonged ethyl chlorid narcosis, Miiller distinguishes four stages, as in all narcoses. The first and second stages are very brief. The re- flexes, however, are lost, and the pupils present exactly the same be- havior as in other narcoses. In the brief narcosis, on the other hand, the pupils continue to react, nor are the other reflexes lost. Herrenknecht,^ whose experience with ethyl chlorid as a narcotic agent was so entirely satisfactory that he earnestly endorsed its employ- ment, distinguished four stages of narcosis, as follows : ( 1 ) The pre- narcotic analgesic stage; (2) the stage of excitement; (3) the stage of deep sleep; (4) the post-narcotic analgesic stage. The first stage, according to Herrenknecht, is chiefly characterized by the diminishing frequency of the pulse and respiration, the deepen- ing of the respiration and the onset of moderate muscular tension. The eyeballs are almost invariably turned upward. The patient is still con- scious, however, and aware of the fact that he is being operated upon, although there is not the least sensation of pain. The hearing is still completely preserved in this stage. The second stage, or stage of excitement, occurred only rarely in the experience of Herrenknecht, and was limited to habitual abusers of al- cohol and to very nervous and excitable patients. As a prophylactic measure, he always administered morphin, or preferably morphin- ^ Boyle: "Practical Anesthetics," 126. " Herrenknecht : ' ' 3000 Aethylchloridnarkosen, ' ' Miinch. med. Woch., 1907, No. 49, 2421. ETHYL CHLORID 263 scopolamin, to patients of this type, prior to the narcosis; and more ethyl chloric! was injected into the mask, in order to hasten the third stage. The third stage is characterized by muscular relaxation, and com- plete loss of reaction to external stimuli; the conjunctival and corneal reflexes have disappeared ; the patient appears as if quietly asleep. The fourth stage resembles the first, except that the patient con- veys the impression of being wide awake; there is no noteworthy pain. The fourth stage is hardly ever absent, not even when the third stage has not been reached and the supply of ethyl chlorid has been stopped, after the onset of the first stage. The end of the fourth stage is recog- nized by the movements of defense on the part of the patient, and the manifestation of pain on operative interference. The signs of complete anesthesia under ethyl chlorid are: (1) A quick, deep, and regular respiration; (2) eyeballs fixed or rolling; (3) face usually slightly flushed; (4) muscular relaxation or rigidity; (5) pupils widely dilated; (6) absence of conjunctival and corneal reflexes. A continuous, safe narcosis is not easily maintained with the present methods. Much cyanosis is a signal for the admission of air or the temporary discontinuance of the anesthetic. Eespiratory embarrassment and spasm of the jaw are common in muscular subjects. Increasing stertor is a signal for more air. The best guide is probably the respiration. If the anesthesia is very deep, cessation of the administration is indicated. It is to be borne in mind that anesthesia is deepened after the administration is discon- tinued, owing to the absorption of the agent from the lower air-passages. The pitlse is usually slow. The signs of an overdose are: (1) Unusually widely dilated and fixed pupils; (2) very great pallor; (3) intermittent respirations or gasping for breath. Elimination. — Experiments were performed by Lotheissen,^ to deter- mine if ethyl chlorid was still demonstrable in the expired air some time after the narcosis. For this purpose, the expired air was passed through a pure concentrated alcoholic solution of potassium hydroxid into water, which was then heated and mixed with a solution of silver nitrate, in order to test for the presence of chlorin. The reaction never occurred when the inspired ethyl chlorid was expired through this appa- ratus; whereas it appeared at once after the direct introduction of even small traces of ethyl chlorid vapor. Upon the basis of these observa- tions, Lotheissen concluded that ethyl chlorid was not breathed out again in the undecomposed state, the chlorin, at least, disappearing from the expired air. But as this air did not possess the odor of mus- ^ Lotheissen: " Aethylchlorid Sauerstoff Narkose," Arch, TcUn. Chir., 1910, 91, 65. 264 ANESTHESIA tard-oil, Lotheissen was of the opinion that a chemical change occurred; perhaps the formation of ethyl thiocarbimide (C3H5NS), for the lungs have a strong reducing power. At any rate, the ethyl chlorid does not remain fixed for any length of time, so that it cannot exert a prolonged narcotizing effect, which means a great advantage in case of threatened asphyxia. The excretion of ethyl chlorid ^ takes place mostly through the lungs; especially in brief narcosis nearly all the vapors are again elimi- nated by the lungs relatively rapidly on account of the looseness of the solution in the blood. The kidneys and other glands enter only very slightly into consideration in brief narcosis, essential amounts of ethyl chlorid being eliminated by those organs only in prolonged narcosis. The very slight solubility in the blood-serum also induces the complete absence of gastric affections, nausea, vomiting, etc., after brief narcosis, for the small quantities in the blood are at once eliminated and do not pass into the gastric juice, or do so only in very minute amounts, devoid of any effect. In prolonged narcoses, larger amounts enter the blood and are also secreted into the gastric juice, giving rise to nausea or even vomiting after awakening. The solubility in the cholesterin-lecithin mixtures, which are formed in the protoplasm of the cells, is also less than with chloroform or ether, for example, so that no such quantities can accumulate in the cells. When the inhalation of new vapors in the narcosis ceases, no new quantities are taken to the cells, but the quanti- ties contained in the cells are reeliminated. However, this elimination can take place only in the quantities which the blood-serum is capable of dissolving. As the cholesterin-lecithin mixtures of the ganglion cells dissolve ethyl chlorid, and therefore accumulate the same during the narcosis, in considerably larger quantity than the blood-serum is capable of dissolving, the narcosis will naturally continue until the last quanti- ties of ethyl chlorid have been eliminated from the ganglion cells. In a brief narcosis, these accumulated quantities are very trifling in amount; after a prolonged anesthesia, however, they reach a certain amount beyond which one must not pass or the patient will die. As ethyl chlorid is only slightly soluble in cholesterin-lecithin mixtures — less than chloroform, for example — this quantity is smaller than what is stored up in the ganglion cells. Nevertheless, after prolonged narcosis, this quantity of ethyl chlorid will suffice to produce after-effects, in the form of vertigo, headache, etc. After-Effects. — Concerning the after-effects of ethyl chlorid upon the animal organism, Konig - states that the result of the examination of the urine of the animals for albumin proved negative in all his experi- ments. Examinations were made a few hours after the narcosis, and on ^ Miiller : Loc. cit. ''Konig, E.: "Die Chloraethylnarkose/ ' Arch. Min. Chir. 1912, 99, 147. ETHYL CHLORID 265 the next day. This serves to show that the ethyl chh)rifl exerts no in- jurious action upon the blood corpuscles and the kidneys, leaving no noteworthy after-effects in this respect. The after-effects occurred in so far, however, as all the animals were found to undergo a more or less considerable loss of body weight, usually about 100 gm., within 8 to 10 days. Several animals suffered from diar- rhea. Eabbits which were narcotized repeatedly, on successive days, or every other day, recovered very slowly from the narcosis; they were ex- tremely drowsy and weak, a considerable time elapsing before the normal condition was reestablished. This observation, as well as the loss in body weight, combined with severe diarrhea, permits the conclusion that ethyl chlorid hardly leaves the organism so rapidly as is generally as- sumed to be the case. Perhaps there occurs a chemical change, namely, a decomposition of the ethyl chlorid in the lung, which organ is said to possess a strong reducing power. It is probable that this was suggested by Lotheissen, who asserted after his experiments that at least the chlorin must disappear from the expired air, as it is no longer de- monstrable in the same. Konig points out that Lotheissen's experiments and conclusions are not tenable, and that these investigations in no way prove a retention of chlorin in the organism. Clinically, the after-effects vary according to the preparation of the patient, the length of the administration, and the method employed. It is conceded by all unbiassed observers that vomiting is one of the com- monest after-effects, occurring in from 15 to 20 per cent of cases. Nau- sea associated with headache occurs in even a greater percentage. The nausea is the same as in ether narcosis, but of shorter duration. It seldom lasts over 15 minutes; in exceptional cases, however, it has lasted 30 hours. ^ Hysterical symptoms may appear in young girls and erotic patients. Erotic thoughts and dreams may occur with this anesthetic as with nitrous oxid and oxygen. {It is for this reason that the anesthetic should never be administered except in the presence of a third person.) Fainting and collapse are sometimes observed. Jaundice has been re- ported in a few cases, showing the effect upon the liver. Albuminuria is absent except in prolonged cases. Fatty degeneration of the kidneys and liver has been noted after repeated administrations. These symptoms may come on in from one to six hours after the administration and may continue for several hours. Collapse is more liable to follow ethyl chlorid than any other anesthetic." This is the principal reason why attempts have never been made at a prolonged anesthesia with this drug. Symptoms of asphyxia appear only with too highly concentrated vapors, or when the inhalation is continued after the onset of prolonged slum- ber; i. e., when the so-called narJcosenbreite (extent of narcosis) is ex- ceeded. ^Hewitt: Loc. cit., 446. ^ Ibid. 266 ANESTHESIA Comparison with Other Anesthetic Agents.- — The narcotic power of ethyl chlorid, when administered by inhalation, mixed with air, is simi- lar to that of ether, and weaker than that of chloroform. Because of the rapidity with which it abolishes consciousness, and the evanescent effects (fugaciousness) of the agent, unless these are forestalled, it is more comparable to nitrous oxid than to either chloroform or ether. Maass,^ who is an opponent of ethyl chlorid narcosis, maintains that, in regard to its absolute danger, ethyl chlorid should be ranked as at least equal to chloroform, for like the latter it may cause heart-death. Eelatively, ethyl chlorid is more dangerous than chloroform, in so far as its desirable as well as undesirable effects are characterized by the rapidity of the onset and the almost instantaneous development to a climax; while the risk of a fatal overdosage is rendered imminent by the smallness of the permissible dose, as well as the impossibility of working in great dilution with air. For this reason, the successive use of ethyl chlorid and chloroform is by no means advisable, as the prepared or suggested injury through the brief ethyl chlorid anesthesia will develop to such an extent in the following chloroform-narcosis, by the summa- tion of the stimuli, as it were, as to endanger the patient's life to an alarming degree, especially as the disturbances concerned in the summa- tion all affect the circulatory system. In a similar way, Maass also considers the beginning of ether narcosis with ethyl chlorid as an added danger. Ethyl chlorid cannot even remotely concur with nitrous oxid, where the effect of the latter suffices, for this gas is very much less dan- gerous than ethyl chlorid. It is better to employ ether, he holds, when nitrous oxid or local anesthesia is not sufficient. The respiration and the heart action are apt to be overwhelmed very suddenly, the ethyl chlorid attacking the body so vehemently that it succumbs before the system can accommodate itself to its action. Ethyl chlorid is appropriate for use in the act of parturition, be- cause the patient's exhaustion permits the production of a relaxed state approaching analgesia with small doses of an anesthetic sufficient for the application of forceps. Another special indication for ethyl chlorid is in war surgery, because soldiers who have been anesthetized with ethyl chlorid awaken sooner and more completely, and thus become fit for transportation, than those who have received ether or chloroform. Furthermore, ethyl chlorid involves less danger of shock than chloro- form, for wounded soldiers suffering from both physical and mental ex- haustion. The advantages of ethyl chlorid as compared with other liquid in- halation, or aliphatic anesthetics, consist in the rapidity with which it produces anesthesia, and the usually complete absence of after-effects, ^ Maass : * ' Chloraethyl als Inhalationsanaesthetikum, ' ' Therap. Monatsh,, 1907, 303. ETHYL CHLORID 267 when properly employed. On the other hand, ethyl chlorid can in no way replace either chloroform or ether, where prolonged loss of sensa- tion is required, its great toxicity strictly forbidding the exceeding of a maximum dose of 5 c.c. Upon the basis of his experience, Herrenknecht ^ concludes that ethyl chlorid is the least dangerous narcotic which we possess at present, not even excepting nitrous oxid. However, it is not applicable for prolonged narcoses, because the scope of the narcosis is evidently not a wide one in the case of ethyl chlorid, and is therefore easily surpassed. It is naturally dangerous when too much is given in a short time of such a highly efficient agent, capable of so rapidly inducing narcosis. The in- halation should be interrupted with the onset of muscular relaxation and disappearance of reflexes. According to animal experiments, and the ex- perience of other observers with patients, respiration usually stops first with ethyl chlorid, followed by failure of the heart action. Hence, im- mediate artificial respiration, perhaps combined with cardiac massage, will probably always prevent a threatened death, as the very volatile com- pound promptly escapes from the body. In spite of the large number of his ethyl chlorid narcoses (3,000) Herrenknecht has never yet been obliged to resort to artificial respiration or stimulation with camphor. Hewitt ^ thinks that ethyl chlorid is far more dangerous than nitrous oxid and distinctly more dangerous than ether, the reason for this being stated as the considerable fall of blood pressure which takes place. Re- garding its safety, Boyle ^ says ethyl chlorid cannot be compared with nitrous oxid and oxygen, and rates its dangers as equal to those of chloro- form. Luke and Ross * state that this drug is safer as an anesthetic agent than ether, chloroform, or ethyl bromid, but that it must not be considered as safe as nitrous oxid. Behr ^ indicates, as special advantages of ethyl chlorid, the relative harmlessness of the drug when used in suitable doses, its pleasant odor, which facilitates its employment, more especially for children, also the absence of a feeling of suffocation and the diminution of the stage of excitement, the rapid induction of anesthesia, the speedy return to con- sciousness, and, finally, the total absence of after-effects. INDICATIONS AND CONTRAINDICATIONS Indications. — In this discussion of the indications for the use of ethyl chlorid no reference will be made to the administration of this * Herrenknecht : Loc. cit. '^ Hewitt: "Anaesthetics," 1907, 135, 444. 'Boyle: ''Practical Anaesthetics," 1907, 141. 'Luke and Ross: 'Anaesthesia in Dental Surgery." Behr: Berl. klin. Woch., 1911, No. 2, 67. 268 ANESTHESIA agent as a preliminary to ether or chloroform, this phase of the subject being considered under each respective combination or sequence. Children, according to all the writers consulted in this connection, are the -best subjects for the administration of ethyl chlorid. It has been used as a routine anesthetic for children five days old and up- ward/ being especially well borne by infants from a few weeks to a few months old. Children of any age, up to about eight years, take this anesthetic, as a rule, without difficulty, losing consciousness and becom- ing quiet in about ten seconds, and giving a satisfactory anesthesia of a minute or a minute and a half. It is preferred by some ^ to any other agent for circumcisions, for example, and for the majority of short operations in children under eight years of age.^ In dental operations upon children, where not more than two teeth are to be extracted, and for removal of tonsils and adenoids, it is advocated.* Luke and Ross,^ Cantlie,^ Mortimer,'^ and many others, consider ethyl chlorid preferable to nitrous oxid for short operations upon very young subjects. Adults present no special indications for ethyl chlorid anesthesia. This agent may be given satisfactorily, however, to very aged and anemic subjects,^ but great care is advocated ° in such cases, the recumbent posi- tion being insisted upon. In patients whose general condition is satisfac- tory, and when the administration is skilfully conducted, ethyl chlorid may safely be employed." For short operations, where greater muscular relaxation is required than is obtainable by nitrous oxid, or where a deeper narcosis is desired, for short examinations or operations in gynecological work, and in brief operations in obstetrical practice, ethyl chlorid may be satisfactorily employed. ^^ Contraindications. — The earlier advocates of ethyl chlorid acknowl- edged practically no contraindications to its use. Girard, for example, according to McCardie,^^ held that circulatory troubles and respiratory affections did not contraindicate its use ; neither age nor sex, nor alcohol- ^ Mortimer: "Anesthesia and Analgesia," 50. -Knight, H. Astley: "Notes on Ethyl Chloride," Brit. Med. J., March 17, 1906, 618. ^McCardie: Loc. cii. * Cantlie, James : ' ' Anesthetics and Surgical Technique. ' ' = Luke and Eoss: "Anesthesia in Dental Surgery," 92. ''Cantlie: Loc. cit., 171. 'Mortimer: Log. cit., 50. 'Luke and Eoss: Loc. cit., 92. " Buxton. "Hewitt: Loc. cit., 441 (1907). "McCardie: Brit. Med. J., March 17, 1906, 617. ^^ Ibid. ETHYL CHLORID 269 ism, nor other intoxications forbade its administration. The only doubt- ful factor was the state of the urinary organs. In a general way it may bo stated that robust, athletic, and alcoholic subjects and confirmed smokers present contraindications to the use of ethyl chlorid, as do likewise persons suffering from chronic or acute diseases. Any obstruction to swallowing renders ethyl chlorid danger- ous. Respiratory affections, whether due to contracted or small air passages, to marked pharyngeal catarrh, or to diseases of the lungs in- volving marked respiratory embarrassment, particularly in the presence of bronchorrhea, are contraindications to the administration of this agent. Feeble heart action, with a probability of fatty degeneration, is given as a contraindication. It is generally conceded that ethyl chlorid is not suitable for oper- ations, long or short, during which absolute muscular relaxation is de- sired. ADMINISTRATION Experimental Data. — According to Konig,^ a careful examination of the available literature concerning the dosage of ethyl chlorid shows the remarkable fact that, up to the present time, no exact dosage has been stated. Very imperfect methods have been employed, which by no means permitted an accurate dosage of the ethyl chlorid in the inspired air. The quantity of the liquid narcotic used is not decisive for the course of the narcosis, but the decisive factor consists in the amount of narcotic vapor which is mixed with the air breathed by the patient, or the laboratory animal ; in other words, the vapor tension of the inspired air. The quantity of narcotic taken up by the blood and the tissue juices, Konig asserts, is dependent upon the ethyl chlorid contents of the in- spired air; the higher the latter (up to a certain degree), the more is taken up by the blood from the inspired air. When constantly new air saturated to the same degree with ethyl chlorid is supplied to the in- dividual, just as much as has already been excreted from the blood will be taken up again. The contents of the blood in ethyl chlorid, there- fore, will be adjusted to a certain standard which is dependent upon the contents of the inspired air in these vapors. In view of the fact that the dose of ethyl chlorid required for nar- cosis (meaning the smallest dose at which narcosis just begins) is not known, Konig endeavored, in a series of experiments, to establish the amount of the smallest narcotizing dose, by the use of accurately meas- ured quantities. It was also important to obtain in all cases a complete narcosis, that is, a narcosis with less of the corneal reflex and relaxation of the muscles. Furthermore, the longest possible duration of the nar- ' Konig: Loc. cit., 147, 270 ANESTHESIA cosis was aimed at, in order to study the effects of ethyl chlorid in ex- tensive narcoses, such as are absolutely necessary for operative purposes. The animals serving for these experiments were frogs and rabbits. The latter were selected for the reason that they are best adapted to experimental investigations, and also because all the experiments for the determination of the narcotizing dose of an anesthetic agent have been almost exclusively performed upon rabbits. The ethyl chlorid of Hen- ning (Berlin) and the preparation of Kahlbaum (Berlin) were used for these experiments. In order to grade the dose with accuracy, it was, of course, necessary for the preparations to be absolutely pure. The purity was determined by passing the ethyl chlorid vapors into water, and ascertaining that this water neither reddened blue litmus paper nor became at once opaque upon acidulation with nitric acid and addition of silver nitrate. A number of experiments were performed on rabbits, using a mask, in order to employ the customary method of narcosis in the human sub- ject. The idea was to obtain a short but deep narcosis, with muscular relaxation and disappearance of the corneal reflex. The customary pro- cedure was therefore exactly followed, meaning that doses of 2 to 5 c.c, averaging 4 c.c, of ethyl chlorid, were administered at the beginning of the narcosis, which was then continued with smaller quantities, 1 to 2 c.c. These narcoses were invariably associated with extreme restless- ness on the part of the rabbits. The most violent tonic-clonic spasms appeared constantly, and were usually increased to an enormous in- tensity. The extremely rapid onset of the narcosis was characteristic of the experiments with the mask; the corneal reflex was usually lost as soon as one minute later, and deep narcosis with complete muscular re- laxation set in. But there again at once appeared the rhythmic twitch- ing, typical for rabbits, independent of the respiration, frequently lim- ited to the extremities, but often involving the entire body of the animal. Chewing spasms, and, in consequence, salivation, as well as opisthotonos and exophthalmos, were almost invariably demonstrable. Eespiration was always extremely irritated. There was severe dyspnea, rapidly in- creasing to such a degree, with concentrated vapors, as to terminate at last in arrest of breathing. On immediate removal of the mask, and in- stitution of artificial respiration, the breathing promptly returned spon- taneously (with the exception of one case), and the animal soon awoke. The awakening always took place very rapidly, after one or two minutes, as a rule, as soon as the animals were supplied with fresh air. Other- wise the narcosis took the usual course of prenarcotic excitement and increased muscular tonus; muscular relaxation in the stage of deep nar- cosis; and another postnarcotic increase of the muscular tonus, with a certain analgesia. The pupils were usually dilated, and the eyeballs were prominent, causing marked exophthalmos. Frequently distinct ETHYL CHLORID 271 cyanosis was demonstrable. These symptoms were due to vasomotor paralysis. Arrest of respiration invariably preceded the stoppage of the heart action, showing that ethyl chlorid, on account of its first stimu- lating and then paralyzing action upon the respiratory center, is not an indifferent narcotic, although the dangerous asphyxia can usually be prevented, or removed, by suitable precautionary. measures. The most important results of Konig's experiments, from the stand- point of the therapeutic employment of ethyl chlorid, are as follows : The smallest narcotizing dose of ethyl chlorid, for cold-blooded animals, is about 2 volume per cent (1.85 vol.) ; for warm-blooded animals, about 4 or 9 volume per cent, respectively. The fatal dose cannot be accurately stated. In cold-blooded animals death was caused with a dose of about 15 volume per cent. The narcotization-zone of ethyl chlorid is ex- tremely wide. Although the facts established upon rabbits cannot all be unconditionally referred to man, the efficient doses for man must be nearly the same as that for rabbits. Methods of Administration. — The authors of this volume are con- vinced, from a review of the literature of ethyl chlorid employed as an inhalation anesthetic, that the best possible method for the administra- tion of this agent has not yet been evolved. Theoretically, the best and safest method of administration is with warmed, moistened, and oxygen- ated vapor of ethyl chlorid. So far as we are aware, this method has not been employed in full, no one having experimented with warmed ethyl chlorid vapor. Under Combinations and Sequences (p. 276) it will be seen that this agent has been employed with oxygen. An appa- ratus could easily be devised for administering the vapor warmed, moist- ened and oxygenated, and in definite amounts, in known percentages of the combined vapors. With these modifications of technique, and with the preliminary use of an alcoholic solution of oil of bitter orange peel, as indicated, doubtless many of the objections to ethyl chlorid as a gen- eral anesthetic might be overcome. Its field of usefulness might like- wise be widened. Hewitt ^ calls attention to two important points in connection with the administration of ethyl chlorid which help to explain the incidence of dangerous symptoms. "In the first place," he says, "ethyl chlorid narcosis is, by the method now in use, so rapidly induced that it is usually difficult or impossible to recognize any stages or degrees in the administration. In the second place, the appearance of the patient dur- ing full narcosis is unattended either by cyanosis or pallor — symptoms which with nitrous oxid and with chloroform respectively indicate that a sufficiently large quantity of the drug has been given. When these two points are borne in mind it will readily be seen that, unless proper care is taken, the limits of safety may readily be overstepped, and that ^Hewitt: Loc. eit., 1907, 442. 272 ANESTHESIA the patient may be plunged, with few if any intervening symptoms, from a safe to a dangerous degree of narcosis. If cyanosis is present it is due to 'overcrowding.' " Open Method. — The open method of administration has nothing to commend it save its seeming safety, which, to the superficial observer, lies in a large intake of an unlimited supply of air together with un- known quantities of ethyl chlorid. An ordinary chloroform mask is placed over the patient's face and ethyl chlorid is administered drop by drop, or a small stream of ethyl chlorid is intermittently sprayed upon the mask until anesthesia ensues. The anesthesia produced in this way seems to be perfectly safe, but cer- tainly no more so than the anesthesia produced by Ware's mask. Anesthesia produced by the open method has been kept up from thirty to forty minutes. Care must be taken to stop its administration immediately upon rigidity or spasm. As long as the respirations are free and clear, there is seemingly no danger from this method. Collapse is less liable to occur after prolonged anesthesia with the open method than with the closed. Milne,^ who reports 600 cases of ethyl chlorid anesthesia, 300 by the open method and 300 by the closed method, from his experience, advo- cates the open method. Malherbe's ^ method of administration is as follows : A handkerchief is held in the palm of the right hand, which is hollowed out to receive it. Into this hollow a jet of chlorid of ethyl is sprayed, 2 to 4 c.c. The "compress" is then firmly applied over the mouth and nose of the patient, who is instructed to breathe deeply. The head and lower jaw are sup- ported with the left hand. "It is absolutely necessary," he says, "not to allow any air to be breathed." Anesthesia is complete in 30 to 40 sec- onds. If the operation is protracted, he renews the dose, claiming that 15 c.c. is sufficient for 15- or 20-minute operations. He also reports, from a colleague, 93 operations, lasting from 8 to 48 minutes, the patients varying from very young infants to two patients over 80 years of age. Semi-Closed Method. — Martin Ware ^ has reported one or two thou- sand cases without a fatality. The apparatus which he used consists of a rubber face-piece, into which a tube three to five inches long is in- serted ; a few layers of gauze are placed between the tube and mask. A stream of ethyl chlorid is directed on the gauze intermittently, thus ap- ^ Milne : ' ' The Administration of Ethyl Chloride by an Open Method, ' ' Brit. Med. J., 1911, 1051. '"■ Malherbe : ' ' Chloride of Ethyl as a General Anesthetic, ' ' Med. Press and Circ, 1911, 91, 461. ^Ware, Martin: Med. News, Aug. 3, 1901; Med. Sec, April 6, 1901. On ethyl chlorid in general anesthesia, see A. M. Dodge: Boston Med. and Surg. J., Feb. 25, 1909, 234. Leighton (St. Louis Med. Bev., Feb. 16, 1907) considers the combination ethyl chlorid-ether an ideal one. ETHYL CHLORID 273 proximating the drop method of chloroform; a layer of hoarfrost quickly forms, due to the freezing of the watery vapor of the expired air. As this frost covers the gauze, a hissing noise is heard as the patient goes into the third stage of anesthesia. If the gauze is entirely covered with ice, the mask should be immediately removed upon inspiration and re- placed again upon expiration. Ware stated that relaxation can be readily secured in children, and also in alcoholics, when a preliminary injection of morphin is given. With neurotics, relaxation is very difficult to secure. He estimated the Fig. 120. — Martin Ware's Apparatus for Administering Ethyl Chlorid. failures at five per cent. By failure was meant a prolonged period of excitation, and, while the patient was seemingly narcotized, the possi- bility of causing muscular rigidity by painfid manipulations. Closed Method. — In order to obtain the best results from ethyl chlorid, it is necessary to employ a rubber bag large enough to receive three or four full expirations, and some arrangement for allowing the ethyl chlorid to enter the bag below so that there may be a very gradual mixture of the ethyl chlorid with the expired air. The connections be- tween the mask and the bag must be large enough not to interfere with respiration in the slightest way. This being so, the small tubes contain- ing 3 to 5 c.c. of ethyl chlorid may be easily attached to a stopcock of any gas-ether apparatus. A rubber tube large enough to hold the glass ethyl chlorid tube securely (admitting the small glass apex of the ethyl chlorid container well into the caliber of the tube) may be attached to the bag as shown in the illustration (Fig. 121). A piece of cotton or gauze must be placed between the end of the glass tube and the bag so as to prevent any glass entering the bag. After the bag has been in- flated by the respirations of the patient, this tube may be broken be- tween the thumb and first two fingers of the anesthetist's hand and the ethyl chlorid allowed to go into the bag. When the closed method is followed, one or two cubic centimeters of ethyl chlorid is sufficient for children, and for feeble and anemic adults. Five cubic centimeters will be found sufficient, as a rule, for adults, alcoholics, and athletes. 274 ANESTHESIA Whether the patient is in the recumbent or sitting position, the head must be on a line with the body, thus insuring an absolutely free air- way. No pillows should be allowed under the head unless some de- formity, such as accompanies rheumatism, will not permit of the head going back. If the operation is one in which the mouth is to be opened, such as extraction of teeth, adenoids, and tonsils, and excision of the tongue, a mouth gag must be inserted before the administration com- mences, otherwise difficulty may be experienced in opening the mouth. It sometimes happens that, even with full surgical narcosis, the masseter muscle may be firmly contracted, making it almost impossible to Fig. 121. — Ethyl Chlorid by the Closed Method. pry the teeth apart. The duration of an administration given by the closed bag and inhaler can be expected to be from one to three minutes. The administration is conducted as follows : Upon expiration, the mask is firmly applied to the face ; upon inspira- tion it is raised slightly, say from % to 14 of an inch from the face, and reapplied immediately, so as to catch the full expiration. In from three to five respirations the bag will be full, when it must be held firmly in place upon the face. The ethyl chlorid tube is now broken and, if at the end of a minute the patient is not completely under the influence of the anesthetic, the end of the bag can be tilted up slightly, when the ethyl chlorid will mix more intimately with the inclosed air. In full surgical anesthesia the muscles are relaxed, with the exception of the masseter, as stated before. The pulse is full and bounding and increased in rapidity. The respirations in an ideal anesthesia are also full and regular but not as full as with nitrous oxid and oxygen, or with ether by the closed method. Usually there is some stertor, the eyes may be fixed and turned downward, the pupils dilated and the lid reflex abol- ished. There is no cyanosis or jactitation. If too large a dose is given or the inhaler is held on the face too long, there may be a rigidity or ETHYL CHLORID 275 opisthotonos. The color should be pink; if cyanosis or spasm is present the mask must be taken off the face and again reapplied. . The average time required to induce anesthesia is one minute. If an anesthesia of from five to fifteen minutes is required, a breath of air should be given and the inhaler reapplied about every four to six respira- tions, with the occasional spraying of a little ethyl chlorid into the inhaler. The method last described, of introducing ethyl chlorid at the bot- tom of a closed bag through a stopcock, was first proposed by Hewitt. Hewitt,^ from the experi- mental work of Konig, and from his own clinical observations, con- cluded that, "as with other anes- thetics, the effects produced by ethyl chlorid primarily depended upon its vapour tension in the at- mosphere presented to the patient. But the last-named observations tend to show that there is no defi- nite percentage mixture the con- tinuous inhalation of which will produce satisfactory results. With percentage mixtures sufficiently weak to be respirable without dis- comfort an unsatisfactory type of anesthesia results; while with mixtures sufficiently concentrated to produce narcosis satisfactorily the initial sensations are so un- pleasant as to prescribe such initial vapour concentration. So far as our present knowledge ex- tends," he continues, "it would seem that, with this anesthetic, the best results are to be obtained by a rational and cautious use of the close system of anesthetization, the vapour being gradually but in- creasingly added to the to-and-f ro respiratory current till anesthesia takes place. We have yet to ascertain whether any special concentration of vapour should be aimed at, after consciousness has been destroyed, and, if so, how such concentration may be secured. We have also to deter- mine by future research the relative influences of the oxygen limitation and the carbonic acid retention which are involved in close methods of administering ethyl chlorid." * Hewitt: Loc. cit., 431. Fig. 122. — Davis Ethyl Chlorid-Ethek- Inhaler: Closed Drop Method. 276 ANESTHESIA From his experience Hewitt found that if ethyl chlorid is admin- istered to adults from an open or semi-open inhaler large quantities of the drug will be needed to bring about even partial anesthesia, the third stage not being attained in many cases. He found that unsatisfactory anesthesia was obtained when attempts were made to administer, by the valveless method, percentage mixtures of ethyl chlorid and air, that is, without rebreathing. When half the amount was given by the valve- less system and the other half by rebreathing, the results were still un- satisfactory. He next tried a definite ethyl chlorid and air mixture diluted with a further unknown quantity of air by the valvular system, — the pure mixture, of known composition, being breathed by the same system, the remainder of the mixture being breathed by the close system. The results were again unsatisfactory, swallowing and shallow breathing characterizing the administration. A measured quantity (5 c.c.) of ethyl chlorid was next given by means of a Clover inhaler, to which was •attached a bag containing 10,000 c.c. of air. The expirations were at first allowed to escape but were retained during the second half of the administration. This method proved more satisfactory than any of the preceding. His final experiments were with the following procedure: "(1) Placing 3,000 c.c. of atmospheric air in a hag; (2) allowing the pa- tient to commence rebreathing this air; and (3) gradually diffusing therein a measured amount of ethyl cldorid contained in a small glass tube connected with the bottom of the bag." With this method the re- sults were satisfactory in thirteen cases in which he first tried it, but sub- sequently it was found to be somewhat less satisfactory than when the patient's own expired air, as opposed to fresh air, was used to partially fill the inhaling bag before the introduction of the ethyl chlorid." For further information relative to the administration of ethyl chlorid, see additional bibliography at end of chapter. Combinations and Sequences. — Somnoform. — Somnoform is a mix- ture of 5 per cent ethyl bromid, 60 per cent methyl chlorid, and 35 per cent ethyl chlorid. It is not so stable as ethyl chlorid, having a greater tendency to decompose, and, like the latter drug, causing head- ache and vomiting. It is very seldom used in this coimtry, pure ethyl chlorid being preferred by the majority of those who advocate ethyl chlorid for any purpose. Anesthol. — Anesthol, which was first employed by Willy Meyer,^ in 1898, is a clear, transparent fluid of a very agreeable odor. It is a ^ Meyer, Willy: "The Improvement of General Anesthesia on the Basis of Schleich's Principles. With Special Eeference to Anesthol," J. Am. Med. Assn., Peb. 28, 1903; ibid., March 7, 1903. Also "The Improvement of General Anes- thesia on Basis of the Principle of Adapting the Boiling Point of the Anes- thetic to the Temperature of the Body (Schleich) — Ten Years' Experience at the German Hospital," Med. Bee, Aug. 15, 1908. ETHYL CIILORID 277 combination ^ of 17 per cent of ethyl clilorid, 35.89 per cent of cliloro- form, and 47.19 per cent of ether. It has a specific gravity of 1.015, which, as Meyer points out, is very close to that of blood (1.05G-1.05!)). Its boiling point is 104° F (40° C). For a further exposition of the principles involved in the making and nse of this preparation see Chapter XX. Meyer's observations with this anesthetic, administered by means of the drop method and an Esmarch inhaler," are as follows : "1. Surgical anesthesia is established in the majority of cases in about eight minutes. If morphin is previously administered, even this time is very frequently reduced by a few minutes. "2. The stage of excitation, if it sets in at all, is of very short duration. "3. Complete anesthesia having been gradually induced, the pulse is full and slow — of the chloroform-anesthesia type — and respiration regular, not stertorous. "4. In no instance has there been an increase in salivation or bronchial mucus during narcosis. "5. The face presents a healthy color. There is no pallor nor cyanosis. "6. If too little of the anesthetic is given, the patient will begin to gag or vomit, as with chloroform; if too much is administered, respira- tion will become shallow, an,d eventually, if still more is poured on the mask, stop altogether, but the pulse will not be interfered with. In other words, the respiratory and not the circulatory center is first affected by an overdose. . . . The tendency throughout the narcosis is toward re- covery from the effect of the anesthetic, not toward a profound anes- thesia. ... "7. After the anesthetic has been stopped, the patient soon comes to, sometimes even while still on the operating table. If he sleeps ^Sollman: "Pharmacology," 437. "The claim that anesthol is a chemical compound, and that its composition does not alter on evaporation, seems to be lanf ounded. ' ' ^ Neef ("Practical Points in Anesthesia") states that at the German Hos- pital it is the practice to employ a Schimmelbusch mask, covered with flannel, over which impermeable cloth, with a lozenge-shaped fenestrum the size of a ten- cent piece, is placed. He also states that it requires 15-20 c.c. for induction, and 40-60 c.c. for narcosis. It is now the routine custom at this institution to administer a hypodermic of morphin, 1 /12 to % gr., one-half to three-quarters of an hour before anesthesia. Cardiac collapse occurs during induction, if at all. This is indicated by weak pulse and pallid face. A change to ether by the drop method will quickly remedy this. When stimulants are needed at any other time, a few drops of ether may be added. With anesthol the volume of the pulse may be expected to decrease about one-third in the course of an hour, and as much as one-half in a two-hour anesthesia. "Crowding" is the cause of sali- vation or Cyanosis during anesthesia, and of excessive vomiting afterward. 278 ANESTHESIA longer, it is usually on account of the previously administered morphin. "8. Vomiting occurs in a small percentage of cases after return to consciousness. It is, however, not of a prolonged or distressing type. "9. Untoward after-effects,^ such as bronchitis, pneumonia, ne- phritis, are not seen as a result of anesthesia with this mixture. A pre- existing catarrh of the bronchi or inflammation of the kidneys may, of course, become somewhat aggravated for a few days, but never to the ex- tent that may happen after the inhalation of other gaseous substances. These complications certainly are never produced by this anesthetic. "10. Patients afflicted with serious valvular cardiac lesions, chronic pulmonary afl'ections, atheromatosis, diabetes, profound anemia, or other complications of serious character have stood this preparation most satisfactorily; contrary to what one would be justified in expecting in such cases, a better circulatory and respiratory condition was induced during anesthesia. "11. The total quantity used is generally small. Our narcotizers very often carry a patient through an anesthesia lasting from one to two hours, with two to three ounces." For further information, especially in reference to the chemistry of anesthol, see Chapter XX. Ethyl Ciilorid and Oxygen. — Lotheissen ^ proposes an improve- ment of ethyl chlorid narcosis by means of the simultaneous inhalation of ethyl chlorid and pure oxygen. For this purpose, he constructed an apparatus which is a modification of the Eoth-Drager apparatus, for hos- pital practice; also a smaller, cheaper apparatus which can be easily transported to the patient's dwelling. This new method of ethyl chlorid narcosis has been used by him for five years past, without unfavorable ex- periences, in about five hundred anesthesias. The usual duration of an- esthesia was ten minutes, only a small number being longer than twenty minutes. The average quantity of ethyl chlorid administered per min- ute amounted to 1 to 2 c.c. with II/2 liters oxygen. In cases concerning habitual users of alcohol, in whom anesthesia could not be obtained within two or three minutes, a few drops of ether were added, resulting in a mixed narcosis of ethyl chlorid and ether with oxygen. In Lotheis- sen's experience, it is not advisable to pass to chloroform or its mixtures after the beginning of the narcosis with ethyl chlorid. In order to avoid asphyxia, in consequence of concentrated vapors, the oxygen is allowed to escape before the ethyl chlorid is inhaled. The pulse-rate and res- piratory frequency are not affected, as a rule. Vomiting is less common than with other narcotics. After-effects are always trifling and transi- tory. Although Lotheissen admits hardly any contraindications, he does ^ Torek, F. : " Anesthol Poisoning Causing Acute Yellow Atrophy of Liver After Operation for Ileo-colic Intussusception," Am. Surg. J., 1910, 52, 489-492. ' Lotheissen : Loc. cit. ETHYL CHLORID 279 not employ the ethyl chlorid-oxygen narcosis in those cases where it is advisable to avoid general anesthesia. Eosenthal and Berthelot ^ have found that a mixture of oxygen and ethyl chlorid, instead of ethyl chlorid alone, produces very satisfactory anesthesia, even to one hour's duration. In 1906 they stated that all the experiments had been conducted upon animals. Ethyl Chlorid and Nitrous Oxid. — Ethyl chlorid has been given by one of the authors (J. T. G;) with nitrous oxid and oxygen in a number of cases, thus securing complete relaxation, otherwise unobtain- able with the latter combination. Ethyl chlorid may be sprayed into the inhaler or through an inspiratory valve. The only objection to using ethyl chlorid in this way is the fact that considerable vomiting occurs immediately after the removal of the mask. Ethyl Chlorid with Ether. — The ethyl chlorid-ether sequence is given in the same way as the nitrous oxid-ether sequence, that is, with any of the closed inhalers. As the patient gets well under the ethyl chlorid, the ether is turned on gradually. The technique of the administration is as follows : Attach a tube containing 3 to 5 c.c. of ethyl chlorid to the stop- cock of the bag by a rubber tube. As the patient fills the bag three- fourths full, break the neck of the tube of ethyl chlorid and thus allow the ethyl chlorid to enter the bag. As the patient sinks under the ethyl chlorid, turn on the ether very gradually. Ethyl Chlorid with Chloroform. — Ethyl chlorid should not be administered preliminary to chloroform, inasmuch as both of these agents are respiratory depressants, both are cardiac poisons, and both act quickly. They have been used in this way, but this sequence should be avoided because it is dangerous. BIBLIOGRAPHY Blumfield : "Eecent Work in the Field of Anesthetics." The Prac- titioner, 1903, 420. Braine, Carter: "The Administration of Ansesthetics in Dental Surgery." Brit. Dent. J., Oct., 1904, 717. Buxton, Dudley : "Operations on the Upper Passages from the Anaesthetist's Point of View." The Practitioner, Jan., 1905, 77. Chaldecott, J. H., and Stephenson : "Ethyl Chloride as a General Anaesthetic in Eye Work." The Ophthalmoscope, April, 1904, 129. Daniells, G. W. B. : "The Administration of Ethyl Chloride." Brit. Med. J., 1904, 949. De Prenderville : "Advantages of Ethyl Chloride Anaesthesia." The Lancet, 1904, 978. ^Eosenthal and Berthelot: Compt. rend., 146, 43. 280 ANESTHESIA Memming, A. L. : "Ethyl Chloride: A Few Practical Remarks." Bristol Med. CUr. J., Sept., 1904, 228. Hatch, E. M. : "Chloride of Ethyl as a Dental and General Anaes- thetic." Brit. Dent. J., Oct., 1903, 638. Hewitt, E. W. : "Anesthetic Effects of Ethyl Chloride." The Lan- cet, 1904, 1408 and 1486. Hilliard, Harvey : "Ethyl Chloride as an Anesthetic in General Practice." The Practitioner, Feb., 1905, 203. Luke, T. D. : "The Use of Ethyl Chloride as a General Ana?sthetic." Edinburgh Med. J., 1903, 425. Lynch, Jerome M. : "The Choice of an Anesthetic in Anal Sur- gery." Va. Med. Semi-Monthly, July 24, 1908. McCardie, W. J.: "Ethyl Chloride as a General Anesthetic." The Lancet, 1903, 952 and 1198. Seelig, M. G. : "Combined Ethyl-Chloride and Ether Anesthesia." St. Louis Courier of Med., Feb., 1905. Ware, Martin W. : "One Thousand Personally Conducted Cases of Ethyl Chloride Narcosis." J. Am. Med. Assn., Nov. 8, 1902. CHAPTER VII CHLOROFORM Chemistry : History ; History of Its Use as an Anesthetic ; Proper- ties; Uses; Preparation of Chloroform; Impurities Liable to Be Present in Chloroform ; Stability of Chloroform ; Decomposition of Pure Chloro- form; Pole of Alcohol in Anesthetic Chloroform; Character of Contain- ers; Stoppers for the Containers; The Changes Which Anesthetic Chloro- form Undergoes When a Current of Oxygen Is Conducted Through It; The Decomposition of Chloroform Vapor Upon Exposure to Gas Light, etc., During Administration; Effect of Agitation Upon Anesthetic Chlo- roform; Standards of Purity for Anesthetic Chloroform. Special Physiology : Effects Upon the Eespiratory System ; Effects Upon the Circulatory System; Effects Upon the Nervous System; Ef- fects Upon the Muscular System; Effects Upon the Glandular System and Other Structures ; Causes of Death from the Administration of Chlo- roform ; Stages of Anesthesia ; Elimination. Indications and Contraindications : Indications ; Contraindi- cations; Af ter-Effects ; Comparison with Other Agents. Administration of Chloroform : Drop Method ; Other Methods of Administration; The Eoth-Drager Oxygen and Chloroform Apparatus; Vernon Harcourt's Inhaler; Junker Apparatus; Braun's Inhaler; Gwathmey Three-Bottle Vapor Inhaler. CHEMISTRY History. — Chloroform, CHCI3 (trichlormethane, methenyl trichlorid, dichlorinated chlorid of methyl, perchlorid of formyl, formyl trichlorid), was independently discovered in 1831 by Guthrie, Soubeiran, and Liebig,^ yet it has been asserted that there are indications of an ear- lier acquaintance with the compound. For example, we are told by Hutman,2 on the authority of Johannes Porta ^ and Sir Walter Scott,^ 1 A fuller historical account may be had in Appendix II, p. 871. 2 J. CJiim. med. (3), 4, 476. ^" Magna Naturalis, " 1619. It should be mentioned here that in 1589 Giau- battista Porta used an essence made from hyoscyamus, solanum, poppy and belladonna, enclosed in a lead vessel, for producing sleep by inhalation of the vapor. * ' ' Letters on Demonology and Witchcraft, ' ' 1830. 281 282 ANESTHESIA that chloroform was known in former times and was then employed as a means of producing insensibility. Investigation shows that this state- ment is based upon misinterpretation.^ History of Its Use as an Anesthetic. — In March, 1847, Flourens announced to, the Academy of Sciences of Paris that chloroform exer- cised on the lower animals an anesthetic action analogous to that of ether. In the same year Doctor (afterwards Sir) J. Y. Simpson, looking for a more convenient and less objectionable anesthetic than ether, consulted Mr. Waldie, a chemist of Liverpool, who suggested that he use chloroform. In November, 1847, he read a paper entitled "No- tice of a New Anaesthetic Agent as a Substitute for Ether in Surgery and Midwifery." From this time on its use spread rapidly. In January, 1848, Hannah Greener, the first victim to chloroform, died at Winlaton near Newcastle, Dr. Meggison being the chloroformist. It may be appropriate to relate exactly under what circumstances she died. The operation was for an ingrown toe-nail. The girl was seated in a chair and only a few whiffs of chloroform were administered, and she died. She was only eighteen or twenty years of age. The history of this first case is given in detail for the reason that so many of the physiological principles relating to chloroform, as we know them to-day, were violated on that occasion, namely : First : It was administered with the patient in an upright posture. Second: It was administered for a minor operation. 1 Most ancient authors who pretend to treat of the wonders of natural magic give recipes for calling up phantoms by the inhalation of certain gases from burning medicated mixtures, generally of oils, and by the use of suffumigations of strong herbs (Hibbert's "Apparitions," 120). The ancient Egyptians, As- syrians, and Chinese were familiar with many vegetable substances (e. g., can- nabis indica) capable of producing ecstatic, sedative, and anodyne effects (Snow's "Chloroform and Other Aneesthetics, " 1858; Bernard's "Lemons sur les anes- thesiques et sur I'asphyxie, " 1875; Lyman's "Artificial Anesthesia and Anes- thetics," 1883; and Dastre's "Les anesthesiques, " 1890). From the "Odys- sey" (iv., 220) we learn that Helen '^cast a drug into the wine whereof they drank, a drug to lull all pain and anger and bring forgetfulness of every sor- row." Herodotus refers to the custom of the Scythians of inhaling the fumes of a kind of hemp; Disscorides (De Med. Mat., iv., 76) makes mention of the prac- tice of boiling in wine the root of the Atropa Mandragora and of administer- ing some of the decoction prior to surgical operations; and Pliny (xxxv., 94) refers similarly to the powers of the mandrake. Mandragora appears to have been used to some considerable extent (Galen, lib. vii., 207; Lucian, "Demos- thenes Ecomium, " 36); it was employed in compounding the "spongia som- nif era ' ' of Theodoric. The Bible and the Talmud also contain references to ancient practices of inducing sleep by artificial means. However, excepting the use of Memphis marble and vinegar as a local anesthetic by the Eomans, carotid compression and (later) mesmerism, vegetable narcotics only were used to as- suage suffering and for the induction of unconsciousness until the foreshadowing of the modern system of anesthesia by the discovery of nitrous oxid. CHLOROFORM 283 Third: It was administered to a patient with high nervous tension. Fourth : It was probably administered in a concentrated dose. Fifth: To a young, vigorous woman. There would be no justifica- tion for such a fatality with our present knowledge. Ten years after its introduction as an anesthetic, Dr. John Snow published his classical work on "Chloroform and Ether Anaesthesia," giving among other things an exact percentage of chloroform and appa- ratus for administration of the same. In 1879 the first committee on the British Medical Association met and condemned the use of chloroform. In 1890, the second Hyderabad committee met and concluded that chloroform was a comparatively safe drug when properly used. In 1901 the British Medical Association committee published a second report condemning the indiscriminate use of chloroform. In the same year Dr. Frederick Hewitt issued a second edition of his work on anesthetics, stating (page 497) that with a com- pound sequence (NoO-Ether-CHCl.,) it is possible to proceed to deep chloroform anesthesia with safety and smoothness. In 1904 one of us (J. T. G.) read a paper at a meeting of the Sur- gical Section of the New York Academy of Medicine, showing that the value of chloroform was more than doubled when used with oxygen in- stead of air, and also stating that this combination was, theoretically at least, safer than ether and air. In 1906 ^ one of the authors of this book (J. T, G.) read another paper before the American Medical Association, drawing attention to the remarkable difference between warm and cold chloroform vapor, and giving reasons why chloroform should be preferred in the Southern States, Cuba, Philippines, and in any of the tropical countries. Properties. — Chloroform is a colorless, limpid liquid, possessing a sweet but somewhat burning taste and an agreeable "ethereal" odor. When absolutely pure, it possesses a density of 1.49887 at 15/4° and boils at -|-61.2° C. Pure chloroform decomposes under certain condi- tions, which will be referred to later, and should never be used for anes- thesia. Anesthetic chloroform does and should contain 0.25 to 1.00 per cent of ethyl alcohol, which acts as a preservative. Therefore anesthetic chloroform may have a specific gravity of not less than 1.476 at 25/25°.- ^ " A Plea for the Scientific Administration of Anesthetics, ' ' J. Am. Med. Assn., Oct. 27, 1906, 47, 1361-1364. 2 The anesthetic chloroform on the American market varies in specific gravity from 1.4730 to 1.4827 at 25/25°, usually in close proximity to 1.476, the mini- mum density permitted by the Pharmacopoeia. The samples of chloroform of German manufacture examined by Baskerville and Hamor {loc. cit.) varied in specific gravity from 1.487 to 1.492 at 15/15°, although one sample possessed a density of 1.497 at this temperature. The specific gravities of the chloroforms recognized as official by the pharmaco- pceias of various countries are given in the following table: (Continued on p. 284) 284 ANESTHESIA When pure, chloroform is not combustible; but when mixed with alcohol, it burns with a smoky flame edged with green. Chloroform is slightly soluble in Avater (0.822 gm. per 100 gm. water at 30° C.) and it imparts to it a sweet taste. It is miscible in all proportions with abso- lute alcohol, ether, benzene, and petroleum spirit. It is soluble to a lim- ited extent in aqueous alcohol. It may be made into an emulsion with water by means of saponin. Chloroform is an important technical sol- vent; it dissolves fats, certain components of india-rubber, resins, sul- phur, phosphorus, iodin, various alkaloids, many alkaloidal salts, as well as many other organic compounds.^ Uses. — Chloroform is used in medicine as an anesthetic," stimulant, antispasmodic, counterirritant, antiseptic ; ^ as an antidote in cases of (Continued from p. 283) DENSITIES AT 15° ACCORDING TO VARIOUS PHARMACOPCEIAS 1.480 1.489 1.490 1.497 1.498 1.500 1.485- 1.489 1.485- 1.490 Spain Portugal Mexico Switzerland Greece Chili France Roumania Germany Denmark Hungary Norway Sweden Finland Belgium 1.485-1.495 1.490-1.500 1.490-1.493 1.490-1.495 1.498-1.500 1.499-1.500 Not below 1.476 at 25° Japan Austria Italy Great Britain Holland Russia United States The chloroform constants according to various editions of the United States Pharmacopoeia are as follows: Date Density at 15° Boiling Point 1851 1.49 142° F. 1869 1.490-1.494 140° F. 1873 1.480 142° F. 1882 1.485-1.490 60-61° C. 1893 Not below 1 .490 60-61° C. 'See, in this connection, Pettenkofer: Jahresber., 1858, 363; Schlimpert: 7bid, 1859, 405; Nowak: Archiv PJiarm. (3), J, 281; Hesse: Pharm. J. (3) ^,649. ^Sir James Simpson: "New Anesthetic," 1847, 7; Illust. London News, Dec. 4, 1847, 370-2; E. B. Simpson: Century, B5, 412; Liv. Age, 66, 720; J. Med. Sci., Sept., 1847; Ed7ib. Medico-Chir. Soc., Nov. 11, 1848; J. Y. Simp- son's "Anesthesia," 1849, 93, 145, 182, 193, 203. * As an antiseptic, chloroform prevents the growth of micro-organisms, but it does not affect the action of soluble ferments (J. Soc. Chem. Ind., 1886, 331). On the antiseptic applications of chloroform, see Eobin: Compt. rend., SO, 52; Au- gendre: Ibid., 31, 679; Barnes: Pharm. J. (3), 5, 441; Salkowski: Chem. Beport., 1888, 166; and Pharm. J. (3), 18, 315, 356, 855. CHLOROFORM 285 strychnin poisoning, and as an analgesic; tccbiiically in ol(!ctrol(;clinics, rubber industry, and piiotograpby ; and in dentistry as a solvent. Preparation of Chloroform.' — Chloroform is made from alcohol, ace- tone, or "methylated spirit," by treatment with chlorid of lime ("bleach"), other hypochlorites, or electrolysis of a halogen salt in the presence of the first mentioned substances. It is also made from carbon tetrachlorid by reduction, the tetrachlorid, as a rule, being previously made from carbon disulphid. Impurities Liable to Be Present in Chloroform.— The impurities liable to be present may be from the variety of materials used in the manufacture of chloroform just noted, and changes the product is liable to undergo on keeping, which will be considered later from chemical and physiological standpoints. Impurities from the Manufacturer. — These are usually the so- called "organic impurities," which are found in considerable amounts in a chloroform which has been made from poorly rectified spirit, acetone, or carbon tetrachlorid (the sources), if impure chemicals have been employed in the manufacture or subsequent rectification and purifica- tion, or if the chloroform has not been properly purified. These im- purities, even though some may not be of much importance from a physiological standpoint, must still be given attention, since an im- pure chloroform is likely to become altered through oxidation during storage, notwithstanding the fact that pure ethyl alcohol has been added. The possible impurities of this class are as follows: Excess water; excess alcohol; acetone; methyl alcohol; carbon tetrachlorid; tetra- chlorethylene, hexachlorethane, etc. ; aldehyds ; amyl, propyl, and butyl alcohols, and compounds; ether "; acids (sulphuric, hydrochloric, formic, acetic) ; metallic chlorids ; ethyl chlorid ; ethylene chlorid ; ethylidene chlorid^; ethyl acetate; oils ("empyreumatic," "pyrogenous," "chlori- nated"); fixed and extractive matter. Purification in Manufacture. — Some of the impurities are washed out with water, others are removed by treatment alternately with concentrated sulphuric acid and sodium carbonate. This product is then further purified by fractional distillation. The details of treatment would be out of place here, however. Interesting facts appear in Appen- dix II, page 871. Impurities Liable from Improper Storage. — Although the ra- tionale of their development will be discussed in later paragraphs, the 1 Further details are given in Appendix II, p. 871. 2 From 1865 to 1875, ether was considered as one of the general contaminants of chloroform. 3 About 1880, ethylidene chlorid was regarded as a general impurity of chloro- form. 286 ANESTHESIxi possible impurities of this class may be conveniently enumerated here. They are : Acetaldehyd ; acetic acid ; formic acid ; carbonyl chlorid ; hydrochloric acid; hydrogen dioxid; chlorin; chlorinated derivatives of alcohol oxidation products. These impurities are dealt with specifically in Appendix II on page 871. Physiological Considerations in Eespect to Impurities. — Huchard ^ has said, "Pure chloroform, well given to a patient prepared for it, almost never kills." Serious results have occurred from the use of anesthetic chloroform containing foreign substances, and although the grades at present sold as chloroform for anesthesia hardly contain suffi- cient impurities which can be held responsible per se for deaths which have occurred during narcosis, yet the presence of these products may account for some, at least, of the disagreeable after-effects so often no- ticeable following the administration of some chloroform.^ Conse- quently, anesthetic chloroform should comply with the most rigid tests,^ and the preparation which conforms with these requirements, and at the same time is comparatively less likely to decomposition than others also answering the same tests, should at all times be preferred to a cheaper but less stable grade. According to the investigations of Feigl and Meier,* the customary chemical examination of a sample of anesthetic chloroform is not conclusive, but requires confirmation by biological tests. Most important, however, is clinical experience. In regard to the fatal results which have been obtained in practice following the use of chloroform vapor for the induction of anesthesia, a considerable percentage of cases, especially those where death has ensued immediately upon first inspiration, may not be due to the action of chloroform at all.'^ However, Simpson ® enumerates a number of cases * J. des. Tract., May 31, 1902. -We have private information as to ill effects from chloroform supplied by- certain dealers. * The pharmacopoeial tests are, in general, insufficient, and samples of chloro- form may comply with the tests prescribed by various pharmacopoeias, and yet important differences may be shown to exist among them by means of other tests. These facts have been brought out by Langaard {Therap. Monatsh., May, 1902). Our opinions will be found in this book. * Biochem. Z., 1906, 316. Feigl and Meier marked out the blood-pressure curves on a drum by means of a kymograph; healthy dogs were made to inhale equal quantities of chloroform of different makes through a tracheal canula. The results obtained showed that the different brands of chloroform, although they appeared almost identical by the chemical tests, differed considerably in their liability to cause a diminution in blood pressure and to cause arhythmia of the pulse beat. 5 See, in this connection, Nussbaum: Eandh, d. allg. p. spec. Chir., 1867, 612; Lawrie: Lancet, 1890, i, 149. 6j?nt Med. J., 1870, i, 199. CHLOROFORM 287 antedating the general introduction of anesthesia which may be classed as "chloroform deaths." ^ In all indubitable cases the nature of the chloroform administered certainly plays an essential role; this fact is supported by convincing evidence, even though the percentage of deaths caused by chloroform administered during operations is unaccountably different in different years, times, and places. We can only attribute the existing diversity of opinion on the subject to the degrees of purity of the anesthetic used, the different modes of administration, the varying lengths of the time of anesthesia, the varying severity of the operation, and the state of the patient. According to almost all authorities, the first danger from the use of chloroform consists in an interruption of respiration,^ and it has been said that only after the observation of the pulse had superseded that of respiration did chloroform deaths become more frequent.^ Ex- perience has therefore clearly shown that every obstacle to respiration must be removed; the presence of irritating contaminants in the anes- thetic must, as a consequence, be guarded against.* In France Sedil- lot,^ who laid the greatest stress on the purest chloroform, did not have to record a single death; but in nine-tenths of all the chloroform deaths on record not a word is said in regard to the article employed, and consequently an important factor for forming an opinion is entirely excluded.® 1 Sansom ("Chloroform," London, 1865) put the average mortality at 0.75 per 10,000; Eichardson (Med. Times and Gas., 1870) at 2.8; and Morgan (Med. Soc. Va., 1872), at 3.4. 2 Metcalfe (Trans. N. Y. Acad. Med., 1, 145) stated in 1850 that his experi- ence, extending then to 800 administrations, went to substantiate the fact that the use of impure chloroform causes headache, nausea, and bronchial irritation. 3 Hewitt: Proc. Boij. Med. and CMr. Soc., 890. * Occhini [Pharm. J. (3), 8, 988] came to the conclusion that the tolerance of chloroform can be assured by the preventive use of ammoniacal inhalations. Although chloroform and ammonia have a mutually antagonistic action on the heart, according to Einger (Practitioner, 1881, 19), such a method is unneces- sary if pure chloroform of anesthetic grade is properly administered to a pa- tient prepared for it. 5 Bull. Soc. CMr., 7, 1881. 6 Some exceptions may be noted here. Dr. Hunter McGuire, surgeon in the Confederate Army during the Civil War, at one time remarked that chloroform had been administered 40,000 times in his corps alone without a single death, and he attributed the result largely to the splendid grade of chloroform which the Union Army had supplied him (almost all the chloroform used by the Con- federate Army was captured from the Federals, although some of English manu- facture came through a blockade.) In 1882 Preston [Pharm. J. (3), 12, 982] recorded that there had occurred 53 deaths in 152,260 administrations, and that in these 53 cases the impure chloroform had something to do with the fatal results. Atthill (Brit. Med. J., 288 ANESTHESIA DuBois-Eeymond ^ appeared to have experimentally demonstrated that impure chloroform is dangerous. Therefore, to the rules for ad- ministering chloroform so often given, he considered that one omitted by all but Sedillot and his school should be added, namely, that the quality of the chloroform be carefully determined and only the very best chloroform procurable be employed for anesthesia. There can be no question but that DuBois-Eeymond obtained re- sults which indicated rather a difference of degree than of kind be- tween the action of pure and impure anesthetic chloroform. He insisted that the impurities act as cardiac depressants ; ^ but, as was noted at 1892, i, 110) stated that he had administered chloroform in over two thousand cases, and considered that it is essential for its safe use that the chloroform be pure; he mentioned that the chloroform in general use at that time was often impure. Chisholm (Sci. Am. Suppl, No. 642, 10,259), who had in 1888 a record of 10,000 cases of general anesthesia with chloroform and no deaths, recorded his experiences, but made no mention whatsoever of the purity of the chloroform used. iBrit. Med. J., 1892, 1, 209. 2 The report of the Hyderabad Commission shows that deaths from chloro- form are more frequently due to its checking the power of respiration than to arrest of the heart's action; see, in this connection. Lancet, 1890, 1, 149, 421, 486, 1140, 1369; 1890, ^, 356. Indeed, Lawrie states (Chloroform, 1901, 15) the doctrine that chloroform has no direct action on the heart must be con- sidered as finally established. This is supported by the results of the bio- chemical observations of Feigl and Meier (BiocJiem. Z., 1906, 316), who con- cluded that narcotic doses of pure chloroform have little or no action on blood pressure, the heart, or the circulatory system in general; and that these effects, when observed, are usually due to accompanying impurities in commercial alco- hol. Some observations, however, seem to indicate that chloroform has an action on the circulatory system, although in these cases the purity of the anesthetic was not always considered. Cf., for example, Filehne and Biberfeld: Z. f. exper. Path. u. Therap., 1906, 3, 171; these investigators discuss the advisability of adding volatile analeptics to chloroform to prevent the reduction of blood pressure. Also, Busquet and Pachon (Compt. rend. Soc. iiol., 66, 90) reported fibrillation of guinea-pig's heart under the influence of chloroform; Schaeffer and Seharlieb (Proc. Physiol. Soc, 1903, 17) have insisted on the specific nature of the action of chloroform on cardiac muscles; and Embley and Martin (J. Physiol., 32, 147) have found that the action of chloroform in the blood in such quantities as may occur with inhalation of 1 to 3 per cent of vapor in air para- lyzes the neuromuscular mechanism of the blood vessels. Tissot {Compt. rend., 142, 234) reported that more than 70 mg. of chloroform per 100 c.c. of arterial blood often causes death. It appears that chloroform forms a loose combination with hemoglobin; for a discussion of the physical chemistry of anesthesia, wherein this is discussed, see Moore and Eoaf: Thompson, Yates and Johnston Lai. Bept. Liverpool, 1905-6, 151-94. Waller (Nature, 76, 403) "tested purified chloroform against the concen- trated residue of its impurities, and found the former to be more powerful than the latter"; he did not, however, lay any stress upon the fact that anes- CHLOROFORM 289 the time/ it does not appear that by their removal pure anesth(?tic chloroform ^ ceases to hamper circulation." That the impurities are ordinarily very slight DuBois-Eeymond admitted, but he contended that, although really infinitesimal in quantity, they act strongly in chloro- form solution. From his experimental investigations and deductions, we learn that there are undoubted impurities which are able to intensify and hasten the lethal properties of chloroform, but we cannot definitely assert Just what these are. We know, however, what the general likely impurities of anesthetic chloroform are; and, if proper precautions are taken to guard against their presence, untoward symptoms should not follow the proper administration of anesthetic chloroform. Stability of Chloroform. — There has been not a little variety of opinion among chemists as to the nature and products of the decom- position of chloroform, especially the changes which chloroform under- goes upon exposure to air ; in fact, this discordance dates from the intro- duction of chloroform as an anesthetic and prevails to-day. This con- dition is ascribable to the many influencing factors occasioned by the degree of purity of the chloroform which may have been under ex- amination, the extent and nature of its exposure; but it is principally due to the failure to consider, and therefrom to correctly interpret, the role of the general variable, alcohol, and with it the accompanying moisture. Decomposition of Pure Chloroform. — The products of the decomposi- tion of "pure" chloroform, according to various investigators, may be thus summarized : thetic chloroform can be of variable quality. Tunnicliffe (Pharm. J., (4), 18, 515) subjected samples of anesthetic chloroform to mechanical shaking for sev- eral days, then exposed them for a considerable time to direct July sunlight, and finally allowed them to evaporate in the laboratory to one-half bulk; the residual portion did not differ at all from pure chloroform in its toxic action on cardiac muscle. iBrit Med. J., 1892, 1, 236. 2 ' * Chloroform Pictet ' ' was taken as the example. ^ See (1) supra, and also Charteris and MacLennan: Brit. Med. J., 1892, 1, 679, who believed that differently manufactured chloroform, although conform- ing to the tests specified by the British Pharmacopoeia, might have different ac- tions, and that possibly some of the dangers were due to the employment of impure chloroform — not by any means an original idea, yet one unique, coming as it did as the expression from a therapeutic standpoint. Therefore, they tested this assumption by administering six different makes of chloroform to guinea-pigs and found that there was a very evident difference in action ex- hibited by the different chloroforms, five of which were of standard British manu- facture. Thus, with ' ' chloroform Pictet ' ' and one chloroform prepared from pure ethyl alcohol, recovery was quicker than with chloroform from rectified spirit, and three other makes from ethyl alcohol, and, further, during recovery no rhythmic tremors were observed. 290 ANESTHESIA Chlorin; Hydrogen chlorid Morson; Maisch; Hager. Carbonyl chlorid Rump; Regnault. Carbonyl chlorid; Hydrogen chlorid. . . . Schoorl and Van den Berg; Dott. Carbonyl chlorid; Chlorin Brown; Schacht and Biltz; Adrian. The formation of carbonyl chlorid alone has been definitely agreed upon. Free chlorin ^ can only result from the photochemical decom- position- of carbonyl chlorid: CQCly "^~~ CO-|-Cl.,. Tihe decomposition of chloroform has been universally conceded to be an oxidation process. The extent of the oxidation is dependent upon the nature of the container, the amount of air present, the purity of the sample, and the intensity of the light to which it is exposed.^ It is likely that, in the cases where chlorin has been identified as an indication of incipient alteration of chloroform, hydrogen dioxid was the real cause of the reactions observed. Role of Alcohol in Anesthetic Chloroform. — With regard to the changes which occur in anesthetic chloroform, that is, chloroform con- taining alcohol, during exposure to air and light, there also existed a decided diversity of opinion,^ principally owing to the fact that no examinations were made during the course of the various investiga- tions, so far as we are aware, for the presence of the oxidation products of alcohol in such chloroform. Some have even regarded the presence of absolute alcohol in chloroform as deleterious.* The whole subject ^ Vide Baskerville and Hamor: J: Ind. Eng. Chem., 4, No. 4. 2 It is generally accepted that chloroform is unaffected by light alone, and that light, although it accelerates oxidation, is not a necessary factor in the process. However, several investigators appear to have inclined to the view that light favors decomposition. In this connection, see Coehn and Decker: Ber. 43, 130; and Weigert: Ann. Fhysik, 1907 (4), 24, 55. The influence of light on the reversible reaction, CO+Cl, -^-^^ COCL, seems to be purely catalytic. The role of any water is that of a true chemical catalyst. The decomposition of pure chloroform is accelerated by light, and carbonyl chlorid is formed with in- creased readiness in the presence of acids. Lowry and Magson {Trans. Chem. Soc, 93, 121) observed that the formation of carbonyl chlorid is evidently accelerated by the presence of acids. 3 DuBois-Eeymond (Sci. Am. Suppl, No. 839, 13, 413) considered that alcohol was of no use when impurities were present and was not necessary when the chloro- form was pure; and Helbing and Passmore {Helbing's Pharm. Record, March, 1892) concluded from the few experiments which they made on the de- composing influence of sunlight on chloroform in the presence of concentrated sulphuric acid that the value of the addition of absolute alcohol to pure chlo- roform was questionable. These investigators assumed that the chloroform which they termed pure contained no alcohol. i Pharm. J., 7, 345. Mialhe found that chloroform acquired "caustic proper- ties" when mixed with a small quantity of absolute alcohol, and concluded that chloroform used in medical practice which caused vesication of the lips and nos- trils contained a certain quantity of anhydrous alcohol, the presence of which was suspected by Soubeiran and Gerdy. Mialhe thought that the alcohol might act by combining with and coagulating the albuminous fluids of the body. CHLOROFORM 291 was therefore carefully investigated by one of us (C B.)' It was also hoped to throw light on, if not fully explain, the role of alcohol ^ and other substances in the so-called preservation of clilorofonn, a satisfac- tory explanation of which had been wanting. Those who have investigated the part played by alcohol in preserv- ing chloroform, up to the present time have held that either chloroform decomposes in the presence of alcohol and that alcohol takes care of the decomposition products, or that the alcohol acts as a "catalytic re- tarding agent" (Stadlmayr). We have definitely shown that the products of the oxidation of anes- thetic chloroform are primarily the oxidation products of alcohol, and that no decomposition of chloroform itself occurs while the oxidation of alcohol proceeds. When the oxidation of alcohol reaches a maximum, decomposition of the chloroform goes on, as in the case of pure chloro- form, with the exception that chlorinated derivatives of the oxidation products of alcohol may result. The decomposition of the chloroform itself is retarded, even prevented, so long as oxidation of the alcohol proceeds, and the retardation is consequently dependent upon the amount of alcohol present. The preservative action of alcohol, first sug- gested by Squibb in 1857 and later (1863) by Brown, independently, is essentially that of a "shunt," and any substance soluble in chloroform and readily oxidizable will exert an inhibitory effect on the oxidation of chloroform itself; for example, sulphur and many other substances.^ 1 Loc. cit. 2 The amounts of alcohol stated as permissible in the various official chloro- forms intended for anesthetic purposes are as follows: Belgium 1.0 per cent. Denmark 1.0 per cent. Sweden 0.5—1.0 per cent. United States 0.6 — 1.0 per cent. France 0.005 part by weight. Italy 0.5 per cent. Switzerland 1.0 per cent absolute. 3 "Inorganic Preservatives." Boettger (Bull, de therap., May 15, 1864) found that chloroform which had undergone decomposition by exposure to sun- light might be purified by agitation with sodium hydroxid, and stated that when chloroform was placed in contact with sodium hydroxid it might be preserved indefinitely. Newman and Eamsay (Lancet, Jan. 23, 1897) recommended a simi- lar treatment, namely, the use of lime, both for purification of decomposed chloroform and as a preservative. Brown (Pharm. J., 61, 669; Mon. Sci., 53, 423), however, found that the method of Newman and Eamsay was unsatisfac- tory. These compounds act by combining with the decomposition products of chloroform. They do not prevent decomposition. Allain (Chem. Ztg., 19, 310) learned that sulphur, purified by digesting for 24 hours with ammonia, and then carefully washed and dried, would effectually prevent the decomposition of chloroform. (In a sample saturated with sulphur, after exposure to sunlight for four months, no impurities could be detected and 292 ANESTHESIA All compounds which have been found to serve as preservatives of chlo- roform are reducing agents, and the effect is only due to their capacity for oxidation. Character of Containers. — Anesthetic chloroform should preferably be furnished in vials, ampules, or bottles of high-grade anactinic the sample produced a "normal anesthesia"). Temoin (Pharm. central., 45, 872; Chem. and Drug., 64, 973) reported that chloroform to which 0.4 per cent of sulphur had been added underwent no alteration on keeping, even when ex- posed to light. This was verified by Dott [Fharm. J., (4), 2, 249], who also experimented successfully with morphin, gallotannic acid, and hypophosphorus acid. "Organic Preservatives." Masson [J. pharm. chim., (6) 9, 568] found that poppy-seed oil exerted a marked preservative action on chloroform. A specimen containing 0.1 per cent was exposed to direct sunlight for 21 days, at the end of which time there was no decomposition; and one with 0.2 per cent of the oil, kept in ordinary light, showed no decomposition in three years. From Masson 's own observations on the preservative powers of alcohol (Masson con- sidered that the preservative action of alcohol on chloroform was demonstrated by the condition of the samples at the Pharmacie Central, in 1899, where speci- mens containing only 0.1 per cent and exposed in yellow glass bottles in a win- dow to diffused light were found to have kept perfectly after standing for ten years), one would conclude that he considered it perfectly satisfactory, Breteau ("French Patent," 1905, 353, 858) devised a method for the pre- vention of the alteration of chloroform in the air and light, and of indicating finally the decomposition, which consisted in adding to the chloroform from 5 to 10 thousandths parts of one of the following bodies: pith of elder, cork of coniferse; and 3 to 5 thousandthss parts of guaiacol, ionone, spermaceti, choles- terol, terpineol, citronellic acid, geranic acid, etc. He stated that the elder pith might be impregnated with a solution of a material colorless in chloroform, and dry, this material, as Congo red, undergoing a change of tint under the influence of the decomposition products of chloroform. Congo red was stated to be very desirable, since it turned blue, and gradually decomposed, when the alteration was decided. Later Breteau mentioned the following substances as preservatives of chloroform in addition to those previously mentioned: ethyl alcohol and ethyl ether, nitrobenzene, methyl and amyl salicylates, thymol, and coniferin. As indicators, he stated that cellulin and gelatin might be used in addition to dyestuflfs and that the indicator might also consist of a dyestuff which changed color in the presence of the decomposition products of chloroform ("First Addi- tion to French Patent," 353, 858, 1905, dated June 30, 1905). Still later he stated that the indicator might be interposed between the chloroform and the stopper of the container, or might be fixed to the stopper, or might even form the stopper. Cinnamic acid and inosite-mono-methyl ether were added to the list of preservative agents ("Second Addition to French Patent," dated Nov. 18, 1905, 358, 858). Breteau and Woog (Compt. rend., 143, 1193) found that, by the use of 2 to 4 parts per 1,000 of oil of turpentine, purified spermaceti, menthol, terpineol, citronellol, geraniol, amyl and methyl salicylates, guaiacol, thymol, safrol, ionone, or methyl-protocatechuic aldehyd, chloroform could be preserved in white glass bottles in diffused light. A number of indicators show the acidity of chloroform undergoing incipient decomposition before it is sufficiently developed to affect silver nitrate. CHLOROFORM 293 glass/ containing about the quantity sufficient for one narcosis, and at the most not more than can be used within several days. If, for any particular reason, chloroform is ordered in a large container, it is ad- visable, immediately after opening it, to subdivide the entire remain- ing contents into two-ounce bottles, taking care to fill the small bottles completely. In no case should chloroform be gradually withdrawn in small quantities from large bottles or carboys. When it is found neces- sary to store anesthetic chloroform it should always be kept in a cool, dark place, in well-filled, or, better still, completely filled, tightly stop- pered bottles of anactinic glass. The keeping qualities of anesthetic chloroform may be seriously affected by the character of containers. The question of keeping anes- thetic chloroform in tin containers has been much agitated in the United States War Department, and within the last ten years this department has decided in favor of the tin container. We (C. B.) be- lieve that glass containers are more conducive to the maintenance of purity for several reasons. First, in cleaning the vessels before filling, any foreign matters present may be readily observed and the bottles properly cleaned. Second, in the case of tins, some of the flux used in soldering may be introduced and thus impart an acid reaction to the chloroform. Hydrochloric acid accelerates the decomposition of chloro- form. The introduction of this flux is also a problem in ether manu- facture which requires the utmost care. Third, we have been informed ^ that "moist chloroform in the pr^seilcl of a metal will slowly form traces of CHaCL and probably . . . that it is possible to distill pure, dry chloroform in a metal container and produce a decomposition, as Shown by the following formula : 4CHCI3 + Cuo = C^Cle + 2CH2CI, + CU2CI2. This reaction, however, takes place so slowly that it would never be noticed except in the handling of a material on which superlative efforts have been expended for years in order to get the last extreme of purity." Moreover, "all chloroform contains traces of CHoClg." Stoppers for the Containers. — The Pharmacopeia of the United States formerly required the use of glass-stoppered bottles,^ but subse- ^ The glass should show no alkaline reaction when the bottle is filled with dis- tilled water containing several drops of plienolphthalein solution and heated at 100° C. for six hours. On the action of alkalies on chloroform, see Berthelot, Bull. Soc. chim., (2), ^9, 4; Andre, Compt. rend., 102, 553; de St. Martin, ihid., 106, 492; and Mossier, Monatsli., 29, 573. It appears to be well established that potassium hydroxid in alcoholic solution will slowly decompose chloroform. 2 By a prominent manufacturer in a private communication. 3 All of the manufacturers of chloroform in this country use brown glass , ("anactinic") bottles. Of the eight different makes of German chloroform that have come into our hands, only two were contained in colorless bottles. 294 ANESTHESIA quently changed this to well-stoppered bottles, thus allowing the use of cork stoppers, a practice which has become general in this country.^ Two objections have been urged against the employment of cork stoppers : First, the chloroform penetrates the cork after some time, especially during the agitation incidental to shipment, causing shrinkage and per- haps leakage.^ The second objection is that organic matter is ex- tracted from the cork, and the chloroform fails when the sulphuric acid test, a test used for the detection of fusel oil, chlorinated decom- position products, etc., is applied. To obviate these difficulties cer- tain manufacturers of chloroform have adopted the plan of covering the bottom of corks with tin foil, a procedure which so far has been found to be satisfactory, but which may be open to some of the objec- tions to tin containers. Other manufacturers use a paper or, parchment covering, and still others select only the best corks and extract them thoroughly with chloroform before use. The Changes Which Anesthetic Chloroform Undergoes When a Cur- rent of Oxygen Is Conducted Through It. — Among the anesthetic mix- tures the combination of chloroform vapor with oxygen was used shortly after the introduction of chloroform as an anesthetic, and it has re- cently been reintroduced into practice by Neiidorfer, Kreutzmann, and others. It is stated by anesthetists that oxygen does not antagonize the action of chloroform on the heart or nerve centers, but that it protects the patient from the dangers which result when chloroform is admin- istered while his blood is in a condition of undue venosity ^ and that it prevents any intercurrent asphyxial condition. Gwathmey has stated positively * that oxygen increases the value of all inhalation anesthetics as regards life.^ 1 In Germany, however, glass-stoppered bottles are used by prominent pro- ducers of anesthetic chloroform. 2 Allain [J. pharm. chim. (3), 9, 571] and Masson [ibid., (6), 9, 568] have recommended that, when chloroform is kept in cork-stoppered bottles, a lute of "bichromate gelatin" should be used to prevent leakage. This is unnecessary when a proper stopper is used, and the employment of lutings on the stoppers has led to differences between the manufacturer and consumer in the past. 3 Buxton: "Anaesthetics," 4th ed., 299. ^ Med. Eec, Oct. 8, 1910, 616. On chloroform-oxj'gen narcosis, see also Zieg- ner: Milnch. med. Wocli., 57, 2585. ^ It has been maintained, however, that chloroform undergoes alteration in this procedure. Falk (Deut. med. Woch., 1902, 862) attempted to demonstrate that the passage of oxygen through chloroform (the purity of this was not de- scribed, but it was evidently of the grade specified by the German Pharma- copoeia) produces chemical changes in the anesthetic. He reported that, after the passage of oxygen for 20 minutes, changes could be recognized in the resi- dual chloroform, in some cases hydrochloric acid and in others an acid having re- ducing properties (acetic acid, resulting from the oxidation of the alcohol in the chloroform used?) having been recognized. The quantities produced were CHLOROFORM 295 We have investigated the changes which anesthetic chloroform under- goes when a current of oxygen is conducted through it. Wc have found that no serious oxidation occurs during the period of anesthesia, and that the oxidation which does occur has to do only with the alcohol pres- ent. Furthermore, it was determined that the oxidation products were entirely removed when the chloroform vapor was swept hy the oxygen cur- rent through water.^ The Decomposition of Chloroform Vapor TJpon Exposure to Gas Light, Etc., During Administration. — The occurrence of untoward symp- toms during the administration of chloroform in rooms in which gas is burning,^ or where there are other varieties of naked flames," or strong electric light * has been reported ; consequently authorities have warned found to be greater the higher the temperature and degree of illumination. This work is partially contradicted by the clinical results obtained by anesthetists, and by the observations of Willcox and Collingwood (Brit. Med. J., Nov. 5, 1910) on the administration of oxygen bubbled through absolute alcohol. They stated that the administration of oxygen bubbled through absolute alcohol is a marked cardiac stimulant. It is especially important to note that they found the admin- istration pleasant and non-irritating to the patient — that it caused no ill-effects to the lungs or bodily system. 1 Baskerville and Hamor, loc. cit. Anesthetic chloroforms containing 0.56 to 1.00 per cent of alcohol and 0.03 to 0.05 per cent of water were used. Oxygen was allowed to flow through 314 to 4 ounces of chloroform in the Gwathmey apparatus at such rates that about half remained in the vaporizer after 3% to 10% hours. The vapors were cooled by a suitable condenser and collected. The examination of the residue and condensed chloroform showed the following: Acidity (acetic acid) : Chloroform used None. Residue in container 0.00015 gm. in 100 c.c. Condensed chloroform None. Sulphuric acid test: Chloroform used Negative. Residue in container Marked reaction. Condensed chloroform Negative. 2 One of the earliest references to the decomposition of chloroform by exposed flames is in the China Med. Missionary J., Dec, 1888, 160. Iterson, Fischer, and Zweifel drew attention to this decomposition in 1889, and in that year Pat- terson narrated personal experiences (Practitioner, 42, 418). See also Lancet, March 12, 1898; Birmingham Med. Rev., Aug., 1892; but especially, Schumburg, Apoth, Ztg., 13, 758; Gerlinger, ibid., 17, 314; and Bisenlohr and Fermi, Ber., 1892, 585. Soubeiran and Liebig had observed that a mixture of chloroform and alcohol in equal measures burns with a smoky flame and pungent odor. According to Ramsay and Young (Jahresber., 1886, 628), the vapor of chloro- form, when passed through a red-hot tube, yields hexachlor-benzene, perchlor- ethane, and some perchlorethylene. 3 Oil lamps and candles. Waddelow, Pharm. J. (4), 6, 324. * Buxton (''Anaesthetics," 1907, 180) states that he observed that chloroform decomposes when a powerful electric lamp is held over the Inhaler. Cf. Schoorl and Van den Berg (Pharm. Weelcblad, do, 47), who show that air is necessary for such decomposition. 296 ANESTHESIA against the performance of surgical operations by gas light. ^ As to just what products are formed there is a difference of opinion. Iterson ^ considered that there occurred a combination of the chloroform vapor with the, combustion gases, whereas Hartman ^ and Waddelow * ob- served an odor of chlorin. Von Langenbeck considered that chloro- carbonic acid was formed, and Breaudat found hydrochloric acid and an acrid oil. At all events, when a mixture of chloroform vapor and air is decom- posed by a flame, irritating compounds are formed.^ Effect of Agitation Upon Anesthetic Chloroform. — Tunnicliffe con- cluded that when chloroform is initially pure, except for added alcohol, it remains free from pharmacological deterioration under the ordinary conditions of military transport, providing that the bottles are kept closely stoppered and protected from strong light. Baskerville sub- jected several samples of chloroform to intermittent agitation for over two hundred hours in a Spiegelberg shaking apparatus and learned that : (1) When anesthetic chloroform is subjected to agitation accom- panied by shock, the alcohol present undergoes oxidation, the extent of this being dependent upon the amount of air present, the nature of the agitation, especially its violence and length, and the light exposure. The experiments were all made in daylight at about 20° C. (2) Impurities decomposable by sulphuric acid are formed under such conditions, these resulting both from oxidation of the alcohol and, when unprotected cork stoppers are used, from the extraction of or- ganic matter from the stopper or luting. "Chlorinated decomposition compounds" may form, although we are inclined to attribute the re- sponse had for their presence to oxidation products of alcohol in this case. Since these conclusions apply to anesthetic chloroform of the present United States Pharmacopana degree of purity and strength, care should be exercised to see, when such chloroform is shipped for considerable dis- tances, or is to be kept in stock on shipboard, that a minimum amount of air is present. Standards of Purity for Anesthetic Chloroform. — There have been instances of sophistication of anesthetic chloroform,*^ and these, while 1 E. g. Von Langenbeck: Pharm. Ztg., April 6, 1889, 221. 2 Ibid. 3 Ibid. * Loc. cit. See also Wardleworth, Pharm. J, (4), 14, 376. 5 Lancet, 1899, 1, 1728; Therap. Gas., 1899, 601; Breaudat 's "Diet, de physi- ologie. " Cf. Ragsky, J. prakt. Chem., 46, 170. 6 Baird (Proc. Mass. Pharm. Assn., 1906, 59) examined six samples of chloro- form in 1904 and found one adulterated. CHLOROFORM 297 rare, have been cases mainly of substitution of commercial chloroform.^ The purity of the drug may be endangered through lack of chemical control in the manufacture or from careless storage. It is quite evident that every sample cannot be tested. Eeliance must be placed upon the integrity of the manufacturers. Confidence in the product, however, may be enhanced by chemical examinations of shipments from time to time. Manufacturers and users will find that compliance with the tests given in Appendix II will insure a drug suitable for anesthesia. SPECIAL PHYSIOLOGY The difficulties encountered in the study of the effects of chloroform upon the organism have been attributed by Gill ^ to the isolation of the phenomena of the physiological action of this agent — in other words, to "the arbitrary separation of prominent phenomena from their inti- mate surroundings." Conclusions should not be drawn from an indi- vidual phenomenon, but from a set of phenomena, or a "state." Gill cites, as an illustration, the phenomenon of pallor, which is a direct manifestation of reflex stimulation of the vasomotor center. It is also a direct result of primary cardiac syncope, and, again, it is a secondary result of stomachic inhibition of the respiratory center. The fallacy of drawing conclusions from pallor alone, without the aid of the accompanying phenomena, is obvious. In considering the special physiology of chloroform, as well as of the other inhalation agents, for purposes of convenience the phenomena have been grouped according to the part of the organism chiefly in- volved. It is to be borne in mind, however, that the effects of chloro- form upon one system of organs cannot be entirely dissociated from its effects upon other systems, and that a given result may be produced by different causes, or by a combination of causes. Inasmuch as the physiological action of inhalation anesthetics in general is based largely upon observations made concerning the effects 1 This appears to have been practiced as late as 1885 in this country, since Davenport [Am. J. Pharm., (4), 16, 111] reported that fourteen out of fifteen samples of chloroform examined by him in that year were the crude article. Chloroform of inferior grade, frequently encountered about 1880 [see Perrin: Pharm. J., (3), 9, 614; and Championniere, ibid., (3), 12, 623], especially in France, is now rarely represented as being of anesthetic grade. This is largely due to the stringency of many of the pharmacopoeias, but is in part to be ascribed to the experience and integrity of the manufacturers. It sometimes happens, however, that chloroform is declared to be impure by surgeons, following a fa- tality from its use in particular, when this is not the case. For an example, see the experiences of Blum: Pharm. J., (4), 19, 103. 2 Gill, Richard: "CHCl. Problem," 1906, 2. 298 ANESTHESIA of chloroform, the discussion of the special physiology of this agent may entail a certain amount of repetition. Effects Upon the Respiratory System. — The effects of chloroform upon the .respiratory system are secondary to, and largely dependent upon, the effects of this agent upon the circulation, low arterial tension being a very important factor. The respiratory system, even to the extent of complete cessation of breathing, is also affected through the action of chloroform upon the nervous mechanism of respiration. When concentrated chloroform vapor is administered, asphyxial symptoms immediately appear, free breathing being suspended from reflex closure of the larynx. With a low percentage of chloroform, according to the experiments of Collingswood and Buswell,^ chloroform quickly produces apnea of a pronounced character. This is not due to diminution of carbon dioxid in the blood, for it can be produced by chloroform mixed with expired air. Chloroform diminishes the ex- citability of the respiratory center to the carbon dioxid stimulus. Buckmaster and Gardner ^ have given a number of plethysmographic tracings to show the lung ventilation during chloroform anesthesia with different percentages of chloroform and ether, and also analyses of the blood gases. They show that with unimpeded respiration under anes- thesia by chloroform given at a slight positive pressure, the ventilation of the lung takes place at a lowered level. During a narcosis in which respiration continues, the lung ventilation is diminished in the first three minutes by about sixty per cent of its original value, and by a similar amount after prolonged anesthesia. They consider that the carbon dioxid content of the blood is reduced below a threshold value by any state of hyperpnea prior to administration of the drug, and this diminution in carbon dioxid content plus the diminished excitability of the respiratory center would suffice to retard or abolish the activity of the center. Gas analyses actually show that with a deep and rapid respiration there is a marked fall in the carbon dioxid content of the blood. They also bring forward evidence to show that the diminution in oxygen content of the blood during chloroform narcosis is not due entirely to diminished alveolar ventilation, but to the action of the drug on the red corpuscles. For further effects of chloroform upon the respiratory system see Stages of Anesthesia, p. 306. Effects Upon the Circulatory System. — The effects of chloroform upon the circulatory system have been made the subject of extensive investigation, from both the experimental and the clinical points of view. The action of chloroform upon the Mood, when administered by in- halation, has engaged the attention of a number of investigators. It is ' Collingswood and Buswell, Proc. Physiol. Soc, 1907, 34. =" Buckmaster and Gardner, London Boy. Soc, Nov. 16, 1911; Nature, 88, 131. CHLOROFORM 299 conceded to have a practical bearing upon the administration of this agent. Gill/ in discussing the relation between chloroform and the blood, emphasizes the point that this relationship is twofold. The negative action of the chloroform causes deoxygenation by diminishing the nor- mal supply of air to the alveoli; its physiological, or physicochemical, action is indirectly the cause of the suspension of the functions of the cerebral centers. The quantity of chloroform vapor that is absorbed may, therefore, be limited to the amount of oxygen requisite to be abstracted fr^m the blood. Inasmuch, however, as the blood, which is directly affected by the physiological action of chloroform, is a variant, and as its actual condition necessarily influences the result that appears in it, it follows, as Gill contends, that each individual example re- quires its own anesthetic degree of chloroform action. Any undue inter- ference with the proper function of the respiratory apparatus tends, by increasing the deoxygenation of the blood, to intensify the action of chloroform. According to Carlson,^ the osmotic concentration of the blood is in- creased during chloroform anesthesia in proportion to the depth and duration of the anesthesia. This is probably due chiefly to the amount of the anesthetic dissolved in the serum. The action of chloroform on the reducing power of the blood has been studied by Lambert and Garneier.^ When defibrinated blood is treated with a current of air containing chloroform vapor, the reducing power of the blood is sometimes increased at once, always after an hour, and this increased reducing power is not due to the dissolution of chloroform in the blood. When, however, defibrinated blood and similar blood containing chloroform are made to circulate respectively through the two lobes of a fresh liver, the glycogen disappears more rapidly in the lobe through which the blood containing chloroform circulates, and at the same time the reducing power of this blood increases more rap- idly than that of pure blood, and in a higher degree than corresponds with the glycogen that disappears. It follows, therefore, that the in- creased reducing power is not due simply to a more active formation of sugar or to a diminution in its rate of consumption. Tunnicliffe and Eosenheim^ studied the action of chloroform on the heart by adding saline fluid perfused through the heart by Locke's method. The depressing action on the heart produced by chloroform was found to be very marked. It was delayed, however, when, in addi- tion to the saline fluid, lecithin was added. The quantity of chloroform iGill: Loc. cit., 254. 2 Carlson: Am. J. Physiol, 21, 161. 3 Lambert and Garneier : Compt. rend., 132, 493. 4Tunnicliife and Rosenheim: Proc. Physiol. Soc, 1903, 15. 300 ANESTHESIA which seriously affected the heart was practically identical with that in the blood in fully narcotized animals. Schaefer and Scharlieb ^ have insisted on the specific nature of the action of chloroform on cardiac muscles. The state of the heart called paralytic dilatation is regarded by them as one of excitatory inhibition ; excitation of the terminal inhibitory mechanism is, however, distin- guished from excitation of the vagus and its endings, and can be brought about by chloroform when the vagus endings are thrown out of action by atropin. The high development of the inhibitory mechan- ism in the heart explains why it, of all muscular tissues, should be most profoundly affected. It is of special interest to note that in the frog chloroform produces contraction of the blood vessels, and not dilatation, as most observers have stated. In the frog used, the central nervous system was destroyed, either entirely or with the exception of the cerebrum. The action of chloroform on the blood vessels has been . studied by Embley and Martin ^ with reference to the kidneys and bowels. They found that chloroform, in the blood in such quantities as may occur with the inhalation of one to three per cent of the vapor in the air, paralyzes the neuromuscular mechanism of the blood vessels. This partly, at least, accounts for the fall of blood pressure which results. These findings are not contradictory to those of Schaefer and Scharlieb, but rather supplement them.^ Vessels in different parts may react in dif- ferent ways to the same poison in different doses. The dilatation is mainly confined to the splanchnic area. It is now generally conceded by clinical observers that a dilatation of the entire cardiovascular system follows the inhalation of chloro- form. The fall of blood pressure is thus accounted for. Tissot * has studied the proportion of chloroform in the organism during anesthesia. In animals rapidly anesthetized by chloroform the amount present in the blood may exceed 50 mg. per 100 c.c, and may reach 70-80 mg. If the anesthesia is slowly induced, it sinks to 45 or even 35 mg. More than 70 mg. per 100 c.c. of arterial Mood often causes death. In the brain the chloroform is in equilibrium with that in the blood. If a fatal result ensues, at the moment of the heart's arrest the amount in the venous blood is more than in the brain, but afterward the amount in the brain is often higher than in the venous blood. The amount in the venous blood is always less than in arterial blood. The length of the period of anesthesia, proportion of chloroform in the brain, and the rapidity of blood circulation are important factors. 1 Schaefer and Scharlieb : Proc. Physiol. Soc, 1903, 17. 2Etnbley and Martin: J. Physiol, 32, 147. 3 Schaefer and Scharlieb : Loc. cit. 4 Tissot: Compt. rend., 142, 234. CHLOROFORM 301 Meyer and Gottlieb ^ have directed attention to the narrow margin between a therapeutic dose and an overdose of chloroform. They found that in deep narcosis, with compensated heart action, the blood content of chloroform is 0.035 per cent, whereas in the blood of a dog anes- thetized to the point of cardiac failure, the chloroform content was 0.058 per cent. The reason for this narrow margin, they hold, is that, in spite of the fact that respiration ceases first, the heart is the .organ primarily affected. This explains why artificial respiration often fails unless the pressure upon the chest is sufficiently forcible to expel the chloroform-laden vapor from the left ventricle. Otherwise the heart continues to be poisoned. The left ventricle, which is principally af- fected in heart failure, was found by Pohl, according to Meyer and Gottlieb, to contain 0.23 per cent of chloroform, whereas the right heart contained only 0.02 per cent. These investigators found, in some of their experiments, that chloroform could be detected in the blood seven hours after cessation of the anesthesia. The danger comes, not from the amount of chloroform contained in the blood, but from its hyper- saturation with the vapor at some one time. Abel - found that in the stage of complete anesthesia the brain con- tains three times more chloroform than an equal weight of blood; blood containing 0.015 per cent, and brain substance 0.0118 per cent. The serum of the blood contains very little chloroform during anesthesia, the greater part that is taken up and carried by the blood being bound to the red and white corpuscles. The effect of chloroform upon the heart itself has been the subject of much investigation and wide diversity of opinion. By some ^ it has been maintained that primary cardiac paralysis occurs only with high percentages of vapor ; by others * it has been claimed that permanent stoppage of the heart is no more likely to occur with high percentages than with low ones. These views have been challenged by those ^ who hold that the heart is never primarily affected, its action being maintained until respiration has ceased. Despite these diverse findings, it is now almost unanimously agreed that chloroform, administered to the degree of surgical narcosis, acts as a direct heart sedative or depressant, and that death occurs as a result of this action. The indirect action of chloroform upon the heart has also given rise to diversity of opinion, particularly with reference to the question of fatality. Whether this action is the indirect result of the irritation by the vapor upon the sensory nerve-endings within the upper air and pul- ^ Meyer and Gottlieb: ' ' Experimentelle Pharmakologie. " ^ Abel : Bull. Johns HopMns Eosp., Jan., 1895. 3 Snow: "On Chloroform and Other Anaesthetics," 1858. 4Comm. Royal Med. and Chir. Soe. ; also, Glasgow Comm, (1879-1880). 5 First Hyderabad Commission, 1891. 302 ANESTHESIA monary passages, giving rise to stimulation of the cardio-inhibitory center, or whether it is a direct result of the effects upon this center of the anesthetic circulating in the blood, has not been determined. The entire subject of cardiac inhibition has been studied experi- mentally by Embley.^ He found that cardio-inhibitory effects are com- mon with atmospheres containing more than two per cent of chloroform vapor. The degree of inhibition increased with increasing percentages of the vapor. His findings with reference to fatal cardiac inhibition are not in keeping with those of the Hyderabad Commission.^ Embley held that slowing or complete inhibition of the heart's action did not occur in animals in which he divided the vagi, and that in order to bring about complete and permanent cardiac inhibition more injury to the heart is necessary than occurs in slight chloroform anesthesia. The Hyderabad Commission, on the other hand, held that animals may be killed by vagus excitation. As Hewitt has pointed out, the possibility and extent of the application of these and similar observations to human subjects are yet to be determined. The vasomotor center is primarily stimulated by chloroform, and does not become paralyzed by the direct action of the agent until the stage of deepening narcosis, when death is imminent. The cause of death from the administration of chloroform has been made the subject of so much experimental and clinical investigation that it has been thought advisable to consider this phase of the action of this agent upon the organism under a special heading. Effects Upon the Nervous System. — According to the consensus of opinion, based upon clinical observation, chloroform produces a pro- gressive paralysis of the central nervous system, the order in which this results being as follows: (1) The higher cerebral centers, involving the intellectual faculties; (2) the lower cerebral centers, involving sensation and motion; (3) the spinal cord, involving reflex action; (4) the medullary centers, involving vital function. For purposes of convenience the above order will be followed in the ensuing brief discussion of the effects of chloroform upon the nervous system. For further data on this subject see the Stages of Anesthesia, p. 306. Effects Upon the Muscular System. — The effects of chloroform upon the muscles of the heart and blood vessels have been discussed under Effects upon the Circulatory System. Muscular spasms are prone to characterize the ordinary administra- tion of chloroform, this tendency being the greater the more vigorous is the muscular development of the subject. The muscles of the extrem- ^ Embley : ' ' The Causation of Death During the Administration of Choloro- form," Brit. Med. J., Apr. 5, 12, 19, 1902. ^ Loc. cit. CHLOROFORM 303 ities, abdomen, chest, larynx, neck, and jaws are particularly apt to be involved in tonic spasms during the earlier stages of chloroform anes- thesia. As anesthesia progresses to the deeper stages, muscular relax- ation follows spasm, as a rule. Sometimes, however, clonic spasms of certain muscles, particularly of the fingers (piano-playing movements), may be noted, the extremities may be involved in slow, coordinated movements, or jerky adductor movements of the arms may occur, pre- sumably as the result of clonic contractions of the muscles of the chest. Spasmodic tongue retraction may occur, giving rise to stertor and stridor. (For the important significance of the muscular phenomena of chloroform anesthesia see Stages of Anesthesia, p. 30G.) Effects TJpon the Glandular System and Other Structures. — The mucous, salivary, and sweat glands are stimulated to hypersecretion dur- ing light chloroform anesthesia. Nicloux and Fourquier demonstrated that chloroform has a special affinity for fat, for liver, kidney, spleen, and nerve tissue, and for striped muscle. According to these investigators the liver of the fetus is even more materially affected than is that of the mother. Thompson ^ conducted a large number of animal experiments, which led to the following conclusions with reference to the kidneys : (1) The volume of urine secreted by the kidneys is affected, as a rule, during chloroform narcosis, in two ways. In the early stages, when the anesthesia is light, the quantity is frequently increased, whereas, during full anesthesia, the secretion is always diminished, and may be suppressed. (2) The after-effect is invariably a great increase, which may reach to four times the normal volume for the same period of time. The maximum outflow may occur about three hours after removal of the anesthetic. (3) The total excretion of nitrogen is, as a rule, greatly increased. The averages taken from experiments with diminished urine volume show that during the anesthetic period the excretion of nitrogen fell to eighteen per cent of the normal, whereas the quantity of urine in the same series fell only to thirty-five per cent of the normal. In a minor- ity of the experiments with increased urine volume, the total nitrogen per period was also increased, but to a much less extent than the volume of urine in the same experiments. (4) The urine secreted during chloroform anesthesia is almost in- variably more dilute (contains a lower percentage of nitrogen) than the normal urine. This holds good even when the volume of urine is dimin- ished. Hence it is inferred that chloroform affects not only the blood ^Thompson: "Anaesthetics and Eenal Activities," Brit. Med. J., Mar. 17, 1906. 304 ANESTHESIA flow through the glomerules, but also the secretion of nitrogenous solids in the tubules, the latter being even more marked than the former. (5) There is a general but not accurate correspondence between urine outflow, kidney volume, and blood pressure. The relationship be- tween the first and second is closer than that between the first and third. (6) In prolonged narcosis, with marked diminution of urine volume, there is a considerable exudation of leucocytes in the renal tubules, which subsequently escape with the urine. The condition is probably produced by more or less vascular stasis in the glomerular vessels. (7) The excretion of chlorids is much increased both during and after chloroform narcosis. In the fourth period, after the removal of the anesthetic, the amount in the urine of the dog may be ten times the normal quantity. (8) Albumin appears in a small proportion of experiments after chloroform inhalation. (9) Eeducing substances other than glucose are almost invariably increased. The nature of the reducing substance has not been definitely determined. Chloroform, according to Apperly's ^ observations, affects the cells of the liver, interfering with the metabolism of fats. The poisonous fatty acids, which cause an acid intoxication, are thus thrown out into the blood. The cells lining the tubules of the kidneys are so damaged that their excretory function is interfered with. As acute infections, espe- cially of the peritoneum, cause changes in the same organs, chloroform should not be given in these cases. According to Delbet ^ and his co-workers, chloroform has a special affinity for the adrenals and checks their functioning. These effects are responsible, they hold, for operative shock and for sudden quiet death in coma after an operation. Delbet injects 0.0004 or 0.0006 gm. epine- phrin subcutaneously at the beginning of the operation, thus rendering anesthesia more regular, diminishing operative shock, and lessening the frequency of sudden post-operative fatalities. If prostration continues, another dose of epinephrin is given the next day. Levy's ^ investigations seem to prove that epinephrin may be safely injected just before induction, or during deep anesthesia, but that a certain definite risk is taken when injection is made during light chloro- form anesthesia. For further discussion of the effects of chloroform upon the glandu- * Apperly, E. E. : " Effect of Chloroform and Ether on Liver and Kidneys in Health and Its Significance in Certain Infective Conditions," Brit. Med. J., Sept. 14, 1912, S, 2698. ^Delbet: Bevue de CMrurgie, 1912, No. 4, 32. "Levy: Brit. Med. J., Sept. 14, 1912. CHLOROFORM 305 lar system, see sections on Elimination, p. 309, and After-Effects, p. 310. Causes of Death from the Administration of Chloroform. — In sum- ming up the action of chloroform upon the organism, Hewitt says ^ : "So far as we have gone, then, it would seem that we have in chloroform a drug which is a powerful protoplasmic poison; which, when given in toxic quantities, leads to death of the organism, not because it paralyzes respiration — for, were it merely a respiratory depressant, artificial respi- ration would be invariably successful in averting death — but because, as recent researches have shown, it markedly depresses the circulation. It is this circulatory depression which renders it difficult to resuscitate patients. The fact that an overdose of chloroform generally paralyzes respiration before the heart's action finally ceases must not be allowed to overshadow the more important fact that, prior to and during the res- piratory failure, the heart has, in many cases, ceased to circulate blood through the organism. Whether in true chloroform toxemia the fatal circulatory failure is principally (a) a failure of cardiovascular origin due to chloroform directly affecting the musculature of the vascular system as a whole; whether it is principally (b) a failure of cardiac origin, the chloroform directly affecting the cardiac muscle relatively more than the walls of the arteries and arterioles; whether it is prin- cipally (c) a failure due to the action upon the nervous mechanism which controls cardiac action; or whether it is principally (d) due to a paraly- sis of the vasomotor mechanism — we cannot at present positively say." According to Gill : ^ "In narcosis which runs its course uncompli- cated by vasomotor, stomachic, or (primary) cardiac disturbance the ultimate cause of death is oxygen-starvation. The respiratory muscles tend to become exhausted, and their failure to act forms a proximate cause: the action of the heart also tends to fail, and cardiac syncope, indirectly induced by the negative action of the agent when in the form of vapor, becomes the intermediary means of the causation of death. The question which fails first, the heart or the action of the respiratory machine, will be decided by the initial condition of the former. If the heart be abnormal, and, in consequence, less able than normally to with- stand increased pressure in its right ventricle, it will fail before the respiration. But if the heart be normal, the action of the respiratory machine will cease before the pulse disappears, because the power of resistance possessed by the respiratory muscles is known to be less than that of the heart." Luke and Ross ^ attribute chloroform deaths to cardiac syncope aris- ing from the following : "^Loc. cit., 1912, 126. 2 Gill, Eichard: "The CHCl^ Problem," 3, Physiological Action, 284. 3 Luke and Eoss: "Anaesthetics," 3rd ed., 192. 306 ANESTHESIA (1) Beflex stimulation of the vagus, causing inhibition of the cardiac pulsations (during light anesthesia). (2) The depressant action of the chloroform on the medullary cen- ter of the heart, the vasomotor center, the intrinsic ganglia, and the myocardium itself (in deep anesthesia from overdose). (3) Cessation of respiration by: (a) Direct obstruction from laryn- geal stertor, or from the falling back of the tongue; (b) Direct retarda- tion and arrest of the pulmonary circulation, first in the capillaries and later in the larger vessels, due to the direct local action of chloroform; (c) Interference with the respiratory center in the medulla, and the subordinate centers in the spinal cord. Stages of Anesthesia. — Under the caption. Factors Which May Be Said to Modify the Physiology of Anesthesia as Ordinarily Induced (p. 63), attention is directed to the fact that, in the experience of one of us (J. T. G.), the phenomena observed during the administration of inhalation anesthetics are modified, to a more or less pronounced degree, by certain procedures now employed by a number of anesthetists. This modification is particularly to be noted in the sequence of events commonly described as stages of anesthesia. It is to be borne in mind, however, that in the present discussion of the physiology of chloroform, as manifested in these stages, reference is made to the administration as ordinarily given, and not with the utilization of the various factors mentioned. Four stages of chloroform anesthesia are usually described. It should be noted, however, that the division of chloroform narcosis into these four stages is more or less arbitrary. Administered by modern methods, with proper care, the induction period is so gradually merged into that of surgical anesthesia that only the keenest observer is able to detect the successive steps. On the other hand, when improperly admin- istered, the induction period passes so quickly into the fourth stage, or stage of overdose, that the anesthetist is unable to detect the danger signals until it is too late. For this reason, it is often stated that death from chloroform most frequently occurs during the initial stage. The First Stage^ or Stage of Light Anesthesia. — The first few drops of chloroform may have no appreciable effect upon the subject, except to stimulate respiration and circulation. If a light vapor (two per cent of chloroform in the air inhaled) is administered, practically no subjective phenomena are noted during this stage, which is of longer duration under these circumstances than when a more concentrated vapor is employed. With the heavier vapor, breath-holding, coughing, resistance to the anesthetic, and other disturbances, such as retching, vomiting, or cyanosis, may occur. The pupil may enlarge, all the senses may become slightly more active, and incoherency of ideas and speech may become apparent. CHLOROFORM 307 Analgesia appears at this stage, but operation should not be under- taken at this time, as the reflexes are often exaggerated, and death may result from reflex cardiac inhibition. An increase in the heart's action and a rise of blood pressure are invariably present. The cerebral centers are affected in this stage. Different subjective sensations, such as ringing and roaring sounds, may be present, usually varying with the vapor concentration, but sometimes occurring despite the careful administration of the vapor. The breathing is usually deep and regular, and the pulse quick and full. The order of disappearance of reflexes during this stage is: (1) superficial skin; (2) vomiting; (3) swallowing; and (4) coughing. The Second Stage, or Stage of Excitement. — This stage should never occur when chloroform is properly administered. (See Adminis- tration, p. 311.) Carelessly employed, however, chloroform anesthesia may be marked by a definite stage of excitement, during which the respiration becomes irregular, the pulse becomes more rapid, there may be struggling, shouting, disconnected talking, crying, and laughing. The face is flushed, and the pupils continue dilated. Muscular spasms, par- ticularly spasm of the muscles of the jaw and neck, chest, and abdomen may occur, indicating the need of air. When the chloroform vapor is too dilute the patient, if a child, may pass into a "chloroform sleep"; if an adult, vomiting may be induced. "False anesthesia" is known to be present when a patient consciously or unconsciously begins breathing automatically, when the anesthetist knows that not enough chloroform has been given to induce full surgical anesthesia. It is best to ignore the pupil and corneal reflexes at this time. If respiration is slow, or if it interferes with the quiet induction of full surgical anesthesia, a few drops of ether upon the mask will usually remedy this trouble. The eyes are poor guides at this time. The pupils are usually widely dilated, the eyeballs may move from side to side, or may be stationary. As the anesthetic is increased in strength, the movements of the eyes become less marked, the muscles relax, and the subject passes into the third stage. Stertor may occur, but is not necessarily indicative of anesthesia. Vomiting will take place if the stage of excitement is unnecessarily pro- longed, its imminence being indicated by feeble, small pulse. The cerebellar centers are now progressively affected. Sensibility to pain is greatly diminished. The patient may answer questions, of which there is no recollection afterwards. There may be unintelligent mutter- ings. With alcoholic and athletic patients it is difficult to induce anesthesia without a conspicuous stage of excitement. By the maintenance of an open airway, by the manipulation of the 308 ANESTHESIA lower jaw in such a way that the presence of an open airway is always apparent, and by the insistence upon absolute silence in the room, the anesthetist may successfully carry a patient from the induction period into full surgical narcosis without any signs of the stage of excitement. The Third Stage, or Stage of Surgical Anesthesia. — In this stage the muscles are relaxed, the pupils contract to normal size, the respiration (this is the principal guide) becomes regular and automatic. Phonation and the conjunctival and corneal reflexes disappear. The pulse rate is lessened, and the face becomes pale. When the pulse rate falls below fifty, and extreme pallor is present, shock is imminent. The pulse should be normal, or a little below normal. When the stage of surgical anesthesia is established, which usually requires from four to eight minutes, it must be maintained. A lighten- ing of the anesthesia may affect the vomiting center. The eyes are usually fixed during this stage, with the pupils con- tracted but responding to light. Hewitt found, by taking measurements with the pupillometer (see illustration, p. 195), that in most cases the pupil, in this stage, measures from two to three millimeters in diameter, usually about two and a half millimeters. Occasionally it remains widely dilated. "A very small pupil (1 to I14 mm.)," Hewitt says, "in most cases indicates a light anesthesia; while a somewhat dilated pupil (31/2 to 4I/2 mm.) usually means either that the anesthesia is very profound, or more probably that the dilatation is of reflex origin and is associated with a light anesthesia." The muscular phenomena of the stage of surgical anesthesia are important danger signals. As previously stated, complete muscular relaxation should accompany this stage. Under the caption. Effects upon the Muscular System, attention is directed to the fact that surgical anesthesia may be accompanied by certain clonic muscular movements, as well as by slow, coordinated movements of certain muscles, and by jerky adductor movements of the arms following spasm of the pectoral muscles. The significance of these phenomena is that they may be taken by the anesthetist or by the surgeon to indicate a lightening of the anes- thesia; in other words, a return to the second stage. If, under this misapprehension, the anesthetic is pushed with a view to obtaining more perfect relaxation and quietude, the subject may be at once plunged into a condition of apnea, which may eventuate in respiratory paralysis and death. The third stage is always marked by a lowering of body temperature. The order of disappearance of reflexes in the third stage is as follows : (1) phonation; (2) conjunctival; (3) corneal; (4) pupil to light; ( 5 ) bladder and rectal. The last two disappear with deepening narcosis. The Fourth Stage, Stage of Deepening IsTarcosis, or Stage of Overdose. — It has been previously stated that the subject may pass so CHLOROFORM 309 quickly from the first stage, or the induction period, into the stage of overdose, that the intervening phenomena, the danger signals, cannot be noted, and. that death supervenes, therefore, during the first few minutes of the administration. The present discussion of the stage of overdose, however, refers not to this state of affairs, but to the more gradual sequence of events, with culmination, through misapprehension of condi- tions, or other exigencies of administration, in what has come to be known as the fourth stage. The ushering in of this stage is indicated by extreme pallor, abolition of all reflexes, and very great relaxation of the muscles. The breathing becomes more and more shallow; the pulse becomes weaker, irregular, and thready. Blood pressure continues to fall. Vasomotor paralysis, sudden or gradual respiratory failure, and complete cardiac inhibition are the final phenomena of the stage of overdose, which thus culminates in death. Elimination. — From studies upon the influence of chloroform on intravital staining with methylene-blue it has been found ^ that, although the results in rabbits were not uniform, evidence was obtained of dimin- ished reduction on the part of chloroformed brains. The increased cir- culation of the dye in the blood is due to the impaired excretory activ- ities of the kidneys and liver. This explains a more abundant passage of the dye into the digestive tract, and the tint of the blood in part accounts for the appearance of the brain. The muscles, however, are less deeply stained than in control animals. The amount of chloroform in the urine of dogs, subjected for pro- longed periods to the anesthetic, has been found ^ to be extremely small, namely, from 6 to 8 mg. per 100 c.c. of urine. The urine after anes- thesia, it has been noted, has a high specific gravity, a strongly acid reaction, and, in 70 per cent of the cases examined by Baldwin ^ (40 in number), there was a marked acetone reaction, due to a disturbance of metabolism, probably in the liver cells. Tests made by Vitali * with urine of four patients, during and after the administration of chloro- form, revealed the fact that chloroform did not pass into the urine, and that the presence in the urine of other organic chlorin compounds could not be detected. This observation is not in harmony with the findings of others,^ who state that the urine may show traces of chloroform, the drug existing in an unchanged state for as long as twelve days after administration. ^Herter and Eichards: Am. J. Physiol., 12, 297. ^ Nicloux : J. pharm. chim., 1906, 24, 64. * Baldwin: J. Biol. Chem., 1, 239. * Vitali: L'Oroso, 22. 5 Thien and Fischer: Deutsch. med. Zig., Dec. 2, 1889. See also Demeraux and Minet: L'Echo med., June, 1904. 310 ANESTHESIA Chloroform is largely excreted through the expired air, according to Meyer and Gottlieb.^ A small part is broken down in the organism, increasing the chlorid content of the urine. INDICATIONS AND CONTRAINDICATIONS The indications and contraindications for chloroform may be cate- gorically stated. For further discussion of the subject see Chapter VIII, Selection of Anesthetic. Indications. — (1) Obstetrical cases, in which the heart is usually hypertrophied and only primary anesthesia is required; (2) young chil- dren, particularly as an introduction to ether; (3) old people, as a pre- liminary to ether; (4) persons afflicted with epilepsy, convulsive seizures of any hind, tetanus; (5) affections of the respiratory system — pul- monary tuberculosis, asthma, emphysema ; (6) aneurysm; (7) pleurisy; (8) operations involving the upper respiratory tract— excision of tongue, inferior or superior maxillae, enlarged glands, or tumors that encroach upon the airway; (9) operations in which the Trendelenburg position is indicated; (10) obese and flabby patients, particularly as an intro- ductory anesthetic; (11) insane patients; (12) operations upon the brain; (13) operations in which the actual cautery is to be used close to the face. Contraindications. — (1) WeaJc, anemic children, with enlarged glands in different parts of the body; (2) status lymphaticus (see Chap- ter VIII, Selection of Anesthetic) ; (3) very prolonged operations ; (4) minor surgery, when a safer anesthetic is available; (5) all opera- tions where, for any reason, the patient is in the sitting posture, or when the body must be raised to this position during the operation; (6) ath- letes and alcoholics who have had no preliminary medication. (7) patients whose general condition is poor, as indicated by a weak, anemic appearance; (8) general septic conditions, especially when due to long- standing tuberculous glands ; (9) diabetic patients; (10) very thin per- sons, not otherwise diseased;^ (11) cyanosis already present; (12) low blood pressure from any cause; (13) the presence of an open flame. After-Eflfects. — The after-effects of chloroform narcosis may be con- sidered under two heads, viz.: (1) immediate, and (2) remote. 1 Meyer and Gottlieb : Loc. cit. 2 ' ' How strong a factor the fat plays is shown by the experiment on hungry animals where the brain takes up much more anesthetic than on well-fed animals in whom the fatty tissues absorb part of such narcotic. From these experiments we can readily imagine the absorption of narcotics by the lipoids of the nervous system during the narcosis and the return of function with their excretion back to the blood and the still further excretion of the anesthetic through the lungs. ' ' Meyer and Gottlieb: " Experimentelle Pharmakologie. " CHLOROFORM 311 Immediate After-effects. — If chloroform is scientifically admin- istered to a patient carefully prepared, and under proper climatic condi- tions, the subject passes into a profound sleep, awakening as from nat- ural slumber. Under other circumstances, however, the awakening may be accompanied by nausea, retching, and vomiting, with pallor and almost imperceptible pulse. Hiccough sometimes proves an annoying after-effect. As a rule, with chloroform, bronchial and pulmonary sequelae are absent. In neurotic and hysterical individuals mental dis- turbances, sometimes amounting to maniacal seizures, may follow. De- lirium of three days' duration has been reported. Aphasia has also been reported as following chloroform. Eemote After-Effects. — Fatty infiltration of all the organs, ac- cording to some observers, follows the prolonged or repeated administra- tion of chloroform. Eatty degeneration of the liver, the heart, and the kidneys is particularly apt to occur under these circumstances, this being the outcome of a direct poisoning of these organs by the drug. Even when given in repeated, very small amounts, chloroform will lead to atrophic cirrhosis of the liver. Albuminuria, acetonuria, urobilinuria, acetonemia, acidosis, which have been noted by various observers as following chloroform anesthesia, are discussed under the special head, Post-Anesthetic Toxemia, in Chap- ter IX, Treatment Before, During, and After Anesthesia. Comparison With Other Agents. — It is important for the anesthetist to bear in mind the relative anesthetic value of the agent. The strength of chloroform as an anesthetic, as compared to ether, is calculated by Hewitt as 6 to 1, by Cushny as 8 to 1. Its anesthetic power is greater than that of ethyl chlorid. ADMINISTRATION OF CHLOROFORM Drop Method. — When chloroform was first introduced by Simpson, the method employed consisted in putting an unmeasured quantity of chloroform on a handkerchief, placing the handkerchief thus treated over the nose and mouth of the patient, and continuing the administra- tion in a somewhat similar manner. Not many years elapsed before the necessity for a different method suggested itself. Simpson then advised that a single layer, of a towel or a handkerchief, should be placed over the patient's nose and mouth, and that the anesthetic be added, drop by drop. This proved to be so much safer than the first way of administer- ing chloroform that the method has been advocated by every ^vriter since that time. Inasmuch as the drop method will unquestionably con- tinue to be employed, and inasmuch as many will continue to use chloro- 312 ANESTHESIA form alone, it is important that the safest method of administration in this way be considered. The Patient.^ — It is more important with chloroform than with any other anesthetic that the head be on a line with the body. If a pillow is placed under the head it should be pushed under the shoulders, in order to prevent asphyxial symptoms during the second stage. This pillow should be removed as the third stage is reached. If in the dorsal position, the head should be turned slightly to one side, the anesthetist holding the symphysis of the jaw with the index finger, the little finger resting upon the carotid artery; the left hand shoiild hold the chloro- form dropper. The clothing should be perfectly loose, shoes and stock- FiG. 123. — The Pilling Chloroform Dropper. ings being removed ; a tight waist or neckband will materially interfere with what might otherwise be a featureless narcosis. If bandages are on the neck or around the waist, these should be cut but not necessarily removed before the operation begins. The Droppek. — It is even more important that chloroform should be dropped from the original container than ether or other inhalation anesthetics ; therefore, containers arranged for dropping should be used. If not so arranged ^ the dropper recommended under ether will serve satisfactorily. Induction. — As the vast majority of chloroform fatalities reported have occurred in the first few minutes of administration, it is most important that the psychical element be controlled as much as possible, both by preliminary medication and by the conversation of the nurses, physicians, or friends who may be near. In addition the anesthetic will go much more smoothly if some Farina colo,gne is dropped upon the ^For general preparation of patient see Chapter IX, Medication, Prelim- inary, During, and Post-anesthesia. "■ Tracings on a smoked drum indicate that the blood pressure is maintained at a much higher level when the anesthetic is induced slowly, as here outlined. CHLOROFORM 313 mask. This should be supplemented in one-half mi mite l)y one or two drops of aromatic spirits of ammonia, or, preferably, of an aleobolic solution of the oil of bitter orange peel.^ The first drop of chloroform can now be administered, and in 30 seconds the second drop, that is, two drops the first minute. This can be increased to six drops the second minute. The third minute, two drops may be given every ten seconds; the fourth minute, three to four drops every ten seconds; the fifth minute, five to ten drops every ten seconds. If the patient is not in full surgical anesthesia at this time, the administration may be con- tinued as follows: eight or ten drops every ten seconds for one or two minutes longer. No time is wasted by beginning the administration of chloroform very slowly. The mucous membranes are, in a measure, blunted, and, if conducted methodically in this way, the surgical stage will be ushered in by the automatic respirations of the patient, the first and second stages not being ob- served ordinarily. Maintaining Surgical Anesthesia. — When the surgical stage is reached the amount necessary to continue the anesthesia will be found to be one- half of the amount necessary to induce anesthesia ; that is to say, if seven drops every ten seconds induce surgical anesthesia in six minutes, three or four drops every ten seconds will easily maintain an even plane of anesthesia. When the third stage is reached, however, it is well for the anesthetist to continue dropping the maximum amount for one or two minutes and then to go back to three drops every ten seconds for the next minute or so, and then to decrease this amount to two, or increase to three or four drops every ten seconds continuously, after that depending upon the patient's reflexes. In surgical anesthesia the muscles are relaxed, the pupil contracts to normal, the respirations (and this is the principal guide) become regular and automatic. The reflexes disappear; the pulse slows down, and, with chloroform alone, the face is usually pale. "A pulse below 50 and extreme pallor are danger signals for the circulation." ^ The respiration is slow, regular, and deep; all motor senses except those of respiration and circulation are completely depressed. It usually requires from four to eight minutes to reach full surgical anesthesia. When surgical anesthesia is finally obtained the patient must be kept in this stage. A lightening of the anesthesia may touch the vomiting ^ See Chapter II, General Physiology. - Meyer and Gottlieb : Loc. cit. Fig. 124.— a Chloro- form Dropper which Should Never be Used. 314 ANESTHESIA center and trouble will immediately follow. The pulse should be normal, or a little below normal ; if oxygen or ether is given, and the anesthetic warmed, it will be normal, or just a little above. The eyes are usually fixed during this stage, with pupils contracted but responding to light unless morphin , has been previously given. When morphin has been given the pupils are contracted throughout. In abdominal operations it is usually necessary to abolish the lid reflex ; where muscular relaxation is not required this reflex may be allowed to remain. In either case the reflex should not be consulted oftener than once every two or three minutes. It must be remembered that patients differ in all of these things. It is best, therefore, to be guided by all available signs, viz.: respiration, circulation, lid and color reflex, and amount of anesthetic given. In the third stage the spinal nerves are affected. With the drop method the face is usually pale, but when administered with oxygen the cheeks are usually flushed and the patient presents a very natural appear- ance. There is usually a reduction of body temperature when given by the drop method, but with warmed oxygen the normal temperature is usually maintained, or slightly raised. Warmed Chloroform. — The chloroform container should be dipped into a pan of hot water, from time to time, to facilitate the vaporization of the liquid. It is much safer to use the drug in this manner. Occa- sionally the mask should be entirely removed from the face for one or two respirations. The anesthetist must anticipate stages by careful observation of his patient. Siirgical anesthesia may be maintained as follows: If three drops are given for ten seconds the patient will grad- ually come out of the anesthetic stage. As the pulse goes up and becomes full and bounding, the color improves and the reflexes become slightly active ; this dosage can be increased to five or seven drops every ten sec- onds for a minute or so. As the reflexes become blunted again the anes- thetist should go back to three drops every ten seconds and continue as before. This method of administration by a watch relieves the anes- thetist of a tremendous nerve strain and enables him to produce a con- tinuous and safe narcosis. In order to determine the comparative value of chloroform as regards life when heated to 100° F., and at normal temperature, a number of experiments were made, using compressed air, and passing this air through chloroform at room temperature, and then to a special animal mask, using a Junker inhaler for the chloroform. Gwathmey ^ found that it took 8.92 -f- minutes on the average to kill (26 animals being used). Employing the same technique, with the addition of another Junker inhaler filled with warm water and placed in a warm receptacle between the chloroform and animal mask, it was found that the average V. Am. Med. Assn., 47, 1361-64. CHLOROFORM 315 time required to kill (using 17 animals) was 20.35 minutes, thus show- ing that chloroform at blood temperature is three times as safe as chloro- form at room temperature. Intermittent Narcosis. — Chloroform should never be administered in the manner sometimes employed, unfortunately, with ether, namely, a small quantity, then a pause, and again a small quantity. The objection urged against the drop method outlined above is that the anesthetist is occupied every second of the time the patient is under the anesthetic. This is, in reality, one of the strongest arguments in its favor, as any untoward signs or symptoms are immediately recognized, and avoidable accidents are not encountered. Color Eeflex. — If the anesthesia has been induced as outlined above, the patient's color will vary according to the individual. If, at any time, a sudden pallor appears about the nose and mouth, it indi- cates shock from some cause, or is a premonitory symptom of vomiting. If the latter, this condition can be immediately rectified by an increased dosage. The anesthetist should touch the forehead or ear of the patient occasionally and note the reflex; i. e., the quickness with which the color returns. This reflex, taken in consideration with other signs to be given below, is a good indication of the heart's action. If the color returns immediately after removing the pressure of the finger, the heart is in good condition. If this reflex is very slow it may not necessarily indi- cate danger ; but it would indicate a weak heart, and possibly dangerous ground. The Pupil. — If morphin has been given as a preliminary medica- ment, the pupil will contract as soon as surgical anesthesia is reached, and usually remain so throughout the operation (this, of course, will depend somewhat upon the action of the morphin in that particular subject). It is unnecessary to attempt any observation of the eye as long as the reflexes are active and the patient is in the second stage of anesthesia. If no preliminary medicament has been given the pupil will be contracted a little below normal. If surgical shock intervenes from loss of blood, or handling important nerves and vessels, or if too light an anesthesia is being maintained, the pupil may dilate. If an overdose of the anesthetic has been given the pupil will also dilate, but will remain in this condition. The difference between the dilated pupil of a light anesthesia and one of an overdose must be determined immediately by the anesthetist. This can be done by recalling the amount of anesthetic that has been given within the last two or three minutes. Conjunctival Eeflex. — In order to obtain the conjunctival reflex, place the index finger upon the upper eyelid and gently separate it from the lower lid. Now press down slightly upon the upper lid and bring the ball of the second finger in contact with the conjunctiva of the upper lid thus exposed. All of this should be done quickly. If the lid closes. 316 ANESTHESIA or if it remains insensitive when considered with the other signs, it will indicate whether or not the necessary plane of anesthesia is being main- tained. Lower Lid Reflex. — This reflex is relied upon by some anesthetists. As the upper lid is separated from the lower, a movement of the lower lid, active, slight, or dulled, would indicate the degree of narcosis. Eyelash Eeflex. — This is obtained by passing the index and second finger quickly over the eyelash of either eye. ■Lid Eeflex. — Many anesthetists merely open the eye, and only deepen the narcosis when closure ensues. This is not quite so sensitive a sign as the lower lid reflex. Eegardless of the eye reflex used, it should not be resorted to oftener than twice in five minutes, or, better still, once in five minutes. One eye should be held in reserve, for if this sign is resorted to by the anes- thetist too often, the reflex becomes either too deadened or too active to be of value. Pulse. — The pulse is most important in chloroform anesthesia. If cold chloroform is administered, a drop of five beats a minute is easily noted. If given warmed, as suggested in this chapter, the pulse will be maintained at a normal rate (see page 314). If anesthesia is induced as indicated, a rise in the second stage need not necessarily be expected. In full surgical anesthesia the pulse should be full and regular; any change in rhythm or fullness should be a warning to the anesthetist. Color refiex must always be considered in connection with the pulse. If no unusual loss of blood or handling of important nerves has taken place, an increase in the volume and rhythm indicates that the patient is regaining consciousness, and is a call for an increase in the amount of anesthetic. A running pulse would indicate shock from some source; an irregular pulse is always an indication of danger. Eespiration. — The respiration is to be more closely watched than any other sign. The respirations should be maintained as full and regu- lar as possible; shallow respiration indicates vasomotor depression, or it may occur just before vomiting, or as one of the signs of shock. Irreg- ular and shallow breathing may be caused by too small an amount of anesthetic. It should be the anesthetist's aim to keep the respirations full and regular. Even when ether is contraindicated as the anesthetic, one, two, or three drops upon the mask for one or two minutes (at the same time continuing the chloroform administration) is a good pro- cedure. If there is an objection to this. Farina cologne, or an occasional drop of aromatic spirits of ammonia, or an alcoholic solution of the oil of bitter orange peel (as in the beginning) may be tried. The gentle rubbing of the lips with a towel, or piece of gauze, will usually stimulate the respiration. The anesthetist must not rely upon any one of the above signs, but must consider each in its relation to the other, and their CHLOROFORM 317 relation to the surgical procedure as a wliole. In this way only can the proper level of anesthesia be maintained. From laboratory and clinical experience, the senior author has been fully convinced for a number of years that the dangers from chloroform are reduced to a minimum so long as the respirations are full and regu- lar, and. the concentration does not exceed 2 per cent. In the intentional killing of hundreds of animals in the laboratory we have failed to see a death from chloroform in which the respirations did not cease before the heart. The only exception to this rule was when the chloroform was given in a very concentrated vapor. This view is confirmed by Hare,^ who states that "the dominant action of chloroform is certainly upon the respiratory centers in the medulla, and that this effect is the cause of death in most cases of chloroform accident. Not only does nearly all ex- perimental work teach us this, but in a collective investigation as to the cause of death under chloroform nearly every case reported was found to have suffered primarily from respiratory arrest." These findings were in- dependently confirmed by Eandall and Cerna in Texas. The only excep- tion to this would be in cardiac disease of any kind, when it can be easily understood that this organ would be the first affected. When we take into consideration that chloroform affects the respiratory centers and, in addition, has direct action upon the heart itself, and that there is also a lowering of the temperature during the administration, it is easily under- stood that, in a long operation,* all three of these factors acting together would readily produce shock of a serious nature. Other Methods of Administration. — The best results have been ob- tained with the Eoth-Drager, or the Gwathmey three-bottle vapor inhaler, or some similar apparatus, in which the percentage of chloro- form is approximately known, oxygen being administered conjointly with the chloroform, and the vapors being warmed through rebreathing. The patients come out of this form of anesthesia in as quiet a state as with nitrous oxid and oxygen. The Roth-Drager Oxygen and Chloroform Apparatus. — The Eoth- Drager apparatus is designed to supply a mixed anesthestic of chloroform or ether vapor, separately or combined, in an atmosphere of oxygen. The face-piece (which is rigid and is suitable for all faces except the edentu- lous) forms an additional mixing chamber, as it admits air which dilutes the oxygen and thus presents an atmosphere richly supplied with oxygen and easily respirable. The percentage of anesthetic vapor is always known, as is also the pressure. The patient merely breathes to and fro into the face-piece, which is kept filled w4th the mixed gases. By gradually increased doses the administrator controls the amount of anes- thetic required at different stages of the operation; if he desires only chloroform, he turns that indicator. If ether is to be added he can easily ^ Bull. Johns Ro'pTiins Hosp., Jan., 1895. 318 ANESTHESIA do so, and regulate the amount of each as the patient requires. The average induction period is six to eight minutes for adults. It is seldom marked by excitement or struggling, and respiration seems free and un- embarrassed. The narcosis is sufficiently profound for all surgical opera- tions requiring relaxation. The apparatus is extremely simple to work, in spite of its somewhat formidable appearance. It produces a satisfactory narcosis without any period of struggling or respiratory distress. Fig. 125. — The Roth-Drager Apparatus. Simple hand apparatus. The after-effects are usually slight, if the anesthetist is careful to limit the amount of anesthetic given. It is clear that the anesthetist is enabled to obtain and maintain an anesthesia which would be either dan- gerous or impossible without the use of oxygen combined with the anes- thetic. Vomiting may occur if too feeble a vapor is given during the induction period. The apparatus delivers three liters of oxygen mixed with five liters of air, which is the volume of gas necessary for the breathing of an adult, that is, eight liters per minute. The falling of the drops of chloroform or ether is both visible and audible. In this way a constant control of the working of the apparatus is possible. The principal points of advan- tage claimed for the apparatus are: (1) The color of the face does not alter; (2) the awakening is infinitely more easy; (3) irritation of the bronchia is reduced to a minimum; (4) the breathing is quiet and regular; (5) depression of CHLOROFORM 319 the pulse does not occur; (G) the pupils remain contracted; (7) re- covery takes place quickly and completely. Chemical investigations show that even in a long narcosis a decom- position of the chloroform does not occur. The anesthetist has both hands free at all times. Statistics of the General Hospital at Liibeck show that the usual amount of chloroform consumed is 391/2 grams for a narcosis lasting Chloroform DRAGERWERK LUBECK tSSm^i Fig. 126. — The Roth-Drager Apparatus. Hand double apparatus. about 40 minutes. The amount of chloroform used with the Eoth- Drager apparatus for the same length of time is 20 grams. The con- sumption of oxygen for 40 minutes amounts to 129 liters. In Figures 125, 126, and 127 the parts of the apparatus are let- tered as follows: M, the main valve of the oxygen cylinder; N", the finimeter, showing the quantity of oxygen contained in the cylinder at all times, and thus rendering a constant control of its contents pos- sible ; 0, a small, easily manipulated valve by means of which the stream of oxygen can be quickly turned on and off; P, an instrument which indicates the number of liters of oxygen used per minute ; Q, the thumb- screw which is turned to perform the dosing of oxygen (P operates in response to Q) ; R, the cock which controls the dose of chloroform ad- ministered per minute ; T, the chloroform in a removable glass which is graduated so as to provide a further means for ascertaining the quantity of chloroform used during each narcosis; V, the gasifier with observa- 320 ANESTHESIA tion glass; L, the economizing apparatus with bag I. L is connected Avith the face-mask l)y a metal hose. The scale of the chloroform cock E, is graduated, the graduations representing drops per minute and grams per minute, so that the strength of the dose being administered can be ascertained by merely looking at the position of the scale. By turning the pointer in another position any change in the strength of the dose can be instantaneously effected. The chloroform reservoir G is kept in position by the arm B. To remove the glass the lever B is pressed downward. The stream- ing of the oxygen causes suction in the glass S. By this means the chloroform is drawn up through the pipe. H and is caused to fall from the drop-former T drop by drop. The drops fall into the stream of oxygen, burst into frag- ments and vaporize. By turning the chloroform the strength of suction can be adjusted at will, and, if desired, can be stopped al- together. Vernon Harcourt's Inhaler. — The improved Harcourt inhaler provides a definite mixture of air or oxygen with chloroform. A maximum two per cent vapor is provided. This is supposed to be the most accurate inhaler ever de- vised for the administration of chloroform. Two colored glass beads are dropped in the chloroform bottle to indicate the temperature ranges between 13° and 15° C. If the temperature of the chloroform is below 13° C, both the colored beads will float. If it is above 15° C, both will sink. The correct temperature is indicated by the blue bead sinking and the red bead beginning to sink. A two per cent chloroform vapor can be continuously administered, or only air may be inhaled. The valves are of delicate mechanism, and easily moved by the inspiration and expiration of the patient. It has been found that with this apparatus a one per cent vapor, or less, is sufficient to maintain an even narcosis in the average run of cases. Hewitt's criticism of this inhaler is as follows :i First: That the current through it depends upon the respiratory action of the patient. ^Hewitt: " Angesthetics, " 1912, 492. Fig. 127. — The Roth-Drager Apparatus. CHLOROFORM 321 Second: That the face-piece pressure, whicli is often necessary in order to obtain proper chloroform percentages, will seriously interfere with the respiration. Third : That its management be- comes irksome to the administrator, particularly in long cases. Fourth : That it cannot be used for many operations. Fifth : It cannot be readily ster- ilized. Sixth : The disadvantage of mak- ing the respiratory pump of the pa- tient act as the pump of the ap- paratus. From the fact that several fatal- ities have been reported while using this apparatus, it would seem that accidents cannot be entirely pre- vented by accurate chloroform per- centages. A comparison of this inhaler with the Eoth-Drager ap- paratus, taking into consideration the appearance of the patient immedi- ately after the discontinuance of the narcosis, would compel us to prefer the Eoth-Drager apparatus. There is no provision in the Ver- non Harcourt inhaler for rebreathing. In addition, no effort is placed upon the respiratory pump by the Eoth-Drager apparatus, as the oxygen Fig. 128. — Vernon Harcourt's In- haler, Complete with Face Piece, Bottle and Beads. FiQ. 129. — Junker's Apparatus. or air with chloroform is forced into the bag under certain, definite pressure. 322 ANESTHESIA Junker Apparatus. — This was the first vapor ^ apparatus devised, and it is especially applicable for adenoid and tonsil work, or any opera- tions about the head where the anesthetist must constantly change his position. The apparatus is so arranged that an approximate maximum of two per cent is reached. The percentage will vary according to the amount and temperature of ether in the bottle and pressure upon the hand bulb. The great advantage of this and all other similar inhalers is that a continuous narcosis can be maintained with the mouth open. (Fig. 129.) The vapor can also be given through nasal tubes directly into the nares, without interfering with the operator. Fig. 130. — Hewitt-Mason's Mouth-Gag with Anesthetic Tubes. Junker's original inhaler consisted of a bottle holding about two ounces of chloroform; this bottle was suspended from the coat of the anesthetist by a hook. A hand-bellows forced air through a tube run- ning through the top of the bottle to the bottom ; air was forced through this tube, and, as it bubbled up through the chloroform, was conveyed to the patient by another tube that merely penetrated the cork; this latter tube was fastened either to a mask or a hollow tube or a nose- piece. It was entirely satisfactory, provided the bottle was not tilted, and that no mistake was made in attaching the rubber tubes from the face-piece and hand-bulb to the tubes entering the top of the bottle. In either event, liquid chloroform would be forced into the upper air passages. Hewitt made a decided improvement upon the Junker inhaler by making it impossible for such an accident to occur. He also de- vised a metal mouth-tube and mouth-gag, after which other mouth- gags, including one of the author's (J. T. G.), have been modeled. (Fig. 130.) Oxygen may be passed through the chloroform by merely attaching the tube from the oxygen tank to the afferent tube leading to the bottle. * The vapor method is one in which air, oxygenated air, oxygen, or other gas passes either over or through the drug, thus vaporizing and delivering the an- esthetic in predetermined percentages. For a discussion of ether vapor anesthesia, see Chapter V. CHLOROFORM 323 Most of the bottles now have compartments for both chloroform and ether, so that the anesthetist can combine the vapors at will. 'J'he ap- paratus was designed especially for operations about the head, neck, and upper air passages, especially operations where the mouth must re- main open for some length of time. Braun's Inhaler. — Braun, of Leipzig, modified Junker's inhaler so that either chloroform or ether alone, or any combination of the two drugs, might be given. A metal mask, without valves, but with a small opening in the top to insure the supply of air, comes with the ap- paratus. Braun's apparatus originated with the idea of giving a con- tinuous anesthesia with highly attenuated ether vapor to which, from time to time, chloroform is added, according to requirements; he thus secures the advantages of both agents and discards their disadvantages. He adds only small amounts of chloroform when the ether vapor is in- sufficient to produce the desired effects. The Braun apparatus is sim- ple and easy to operate, and has decided advantages over the Harcourt inhaler. Gwathmey Three-Bottle Vapor Inhaler. — The apparatus is a modifi- cation of Braun's, with the addition of a water bottle, through which all the vapors of chloroform and ether must pass before getting to the patient. In addition, in cold weather, a heater is used to warm the anesthetic to the temperature of the blood. With this apparatus air or oxygen can be increased or decreased without, at the same time, de- creasing or increasing the anesthetic vapor. The apparatus consists of three six-ounce bottles. In the ether and water bottles the end of the tube is flattened out so as to get the maximum amount of vaporization; the smaller bottle, containing a little over one ounce, is placed within the large six-ounce bottle marked "chloroform." The tube in the chlo- roform bottle is perfectly straight. It is estimated that with the mask used a two per cent maximum vapor is obtained. Pure ether, chloro- form, or a mixture of these anesthetics, may be given by simply turn- ing one stopcock on the top of the metal holder. (See p. 33.1:.) CHAPTER VIII THE SELECTION OF THE ANESTHETIC AND TECHNIQUE FOB SPECIAL OPERATIONS Conditions Affecting Selection : Inhalation Anesthetics ; Safest Anesthetic; Chloroform with Oxygen; Value of Combinations and Sequence in Anesthetics ; Safest Sequence. EuLES to Be Observed in Selecting the Anesthetics: Age; Heart Disease; Pulmonary Tuberculosis; Obese Patients; Thin Subjects; Athletes, Alcoholics, and Other Drug Habitues; Diseases of the Lungs; Kidney Diseases; Cancer; Nervous Patients; Epileptics; Insane Pa- tients; Status Lymphaticus. Special Operations : Short Operations ; Nitrous Oxid ; Ethyl Chlorid; Chloroform and Ether; The Mastoid; The Upper Respiratory Tract; Excision of the Tongue; Cleft Palate; Submucous Operations; Adenoid and Tonsil Cases; Tracheotomy; Goiter (Angina Ludovici, Ex- ophthalmos — Graves' Disease) ; Amputations; Operations Upon Fingers and Toes; Circumcision; Rectal Cases; Obstetric Cases; Curettage; Genito-urinary Operations; Laparatomy; Gastro-enterostomy and Simi- lar Operations ; Peritonitis or Intestinal Obstruction. Conclusions. Bibliography. CONDITIONS AFFECTING SELECTION In selecting an anesthetic for a given operation many things must be considered. First of all, the safety to life. Then the applicability of other anesthetics to the patient, whose size, age, habits of life, and con- dition at the time of operation must all be considered. The surgeon's likes and dislikes also demand attention. If he is accustomed to using chloroform, with its quiet breathing and subdued pulse, he will not be satisfied with ether, with its quick, bounding pulse and rapid respira- tion. Some surgeons object seriously to a patient moving, although this movement may not interfere with the operation. The very fact of the patient's moving may cause him to become nervous and thus prevent him from doing his best work. Again, other surgeons like a light anes- 324 ANESTHETIC AND TECHNIQUE FOR SPECIAL OPERATIONS 325 thetic, and those who have adapted themselves to nitrous oxid and oxygen may not be pleased with chloroform with its absolute quiet and relaxation. Inhalation Anesthetics. — A list of anesthetics, their combinations and sequences, is therefore desirable. The following list, as regards safety to life, is based upon original experiments made, in 1904, by one of the authors (J. T. G.) : 1, Nitrous oxid with oxygen; 2, nitrous oxid with air; 3, ethyl chlorid with oxygen; 4, ethyl chlorid with air ; 5, anesthol with oxygen ; 6, ether with oxygen ; 7, chloroform with oxygen; 8, ether with air; 9, C. E. mixture (chloroform two parts, ether three parts, and oxygen) ; 10, C. E. mixture with air; 11, chloro- form with air. Safest Anesthetic— Nitrous oxid with oxygen is easily the safest anesthetic known. It is almost impossible to kill normal animals with this combination. If they are asphyxiated, and the mask is removed, the heart will continue to beat for several minutes. This gives suffi- cient time for the gas to escape as it reaches the lungs, and for breath- ing to commence again automatically. Such is the case in the labora- tory and in the operating room. The only likelihood of a mistake is when the physiological signs of asphyxiation are not known. Chloroform with Oxygen. — While chloroform is classed as the most dangerous anesthetic, generally speaking, the purity of the chemical, the mode of administration, and the environment may considerably alter its place in the list. If used with oxygen, and in definite per- centages, it is safer for certain cases (i. e., patients with abnormally narrowed air passages) than is nitrous oxid with oxygen. Again it is safer in tropical countries and in the summer time than in a colder cli- mate or during the winter. The patient's physique may be such that it would be very difficult, if not impossible, to administer nitrous oxid with oxygen alone. Value of Combinations and Sequence in Anesthetics. — Again, the relative safety of these anesthetics is enhanced by using them in proper combination and sequence. The following is a list of the usual com- binations and sequences: (1) Nitrous oxid with oxygen, combined with warm ether. (3) Nitrous oxid with oxygen, combined with ethyl chlorid (either closed or open). (3) Nitrous oxid-ether sequence. (4) Nitrous oxid-ether sequence (closed method), followed by ether. (5) Nitrous oxid-oxygen-ether sequence (vapor or drop). (6) Nitrous oxid-ether sequence, followed by ether and chloroform. (7) Nitrous oxid-ethyl chlorid-ether sequence (closed method). (8) Ethyl chlorid-ether sequence. (9) Ethyl chlorid, ether-chloroform sequence. 326 . ANESTHESIA (10) C. E. mixture-ether sequence. (11) C. E. mixture-ether-chloroform sequence. (12) Chloroform with ether sequence (vapor or drop). (13) Chloroform ether-chloroform sequence (vapor or drop). (14) Chloroform-ether (vapor or drop), followed by ether (closed method). (15) Ether-chloroform sequence. (16) Ether-chloroform-ether sequence. Safest Sequence. — The latest and best development in "anesthetics is the use of ether and chloroform in combination with nitrous oxid with oxygen, making nitrous oxid and oxygen the basis of the anes- thesia. It has also been found by clinical experience that what is com- monly known as the gas-ether sequence, — that is, giving first gas from one to two minutes, and then switching to ether, — is the best method of administering ether in suitable cases. (See page 218.) The gas-ether- chloroform sequence is a still further modification of the above, and for certain cases it is probably the best sequence. ISTo hard-and-fast rules are to be laid down, however, for the selection of the anesthetic, for the method of its administration, or for the time of changing from one anesthetic to another. This must be learned by experience, and the anesthetist must know the physiological effect and the dosage of each drug that he uses. The fact that these anesthetics are used in combination and se- quence by the most expert anesthetists of to-day is good evidence that in many cases no one agent is suitable throughout the anesthesia. It is unwise to suggest or recommend this or that special anesthetic or method, as, for example, ether by the drop method, for this seems like an attempt to fit the anesthetic to the anesthetist rather than to the pa- tient. RULES TO BE OBSERVED IN SELECTINCt THE ANESTHETIC Some definite rules serve to guide us in the selection of a suitable anesthetic. Age. — Infants. — Children under one year of age should never be kept under the anesthetic longer than one hour. Many children have been successfully anesthetized for one or two hours at a delicate age, but a certain definite risk is incurred when the anesthesia lasts one hour or more for a child under one year old. Until within recent years it has been the custom to administer chloro- form to children. A number of deaths have been reported of children dying two or three days after the administration of chloroform, and post- mortem examination has revealed the fact that these children had what is known as status lymphaticus. (See page 331.) "The clinical evi- ANESTHETIC AND TECHNIQUE FOR SPECIAL OPERATIONS 327 deuces of this condition do not allow its certain detection beforehand, but the anesthetist will be wise to be particularly on his guard when the patient is a child or young adult of slight physique, though good height, pale complexion, timorous disposition, or with large tonsils and adenoids. If the spleen is palpable and there are palpably enlarged cervi- cal or abdominal glands, apprehension is still better founded. Lymphoid follicles visible on the epiglottis and much enlarged papillae at the back of the tongue are also evidences suggestive of the condition." ^ On this account it is now customary to administer ether alone or the C. E. mixture. If chloroform is given at all to very young children, it should be ad- ministered warm, and preferably with oxygen instead of air. Chloroform should not be entirely abandoned for children or other subjects because it has been misused in the past. It is unquestionably safer and better to induce the anesthesia with chloroform in the majority of instances and to maintain the anesthesia with ether than to shock the child by attempting to commence the anesthesia with ether. It is always best to begin the anesthesia with one or two drops of the essence of bitter orange peel (25 per cent TJ. S. P.), or any cologne, provided it is not sweet smelling. Any sweet perfume or scent tends to produce vomiting at this time. There are a very few conditions in which the anesthesia should be maintained with chloroform. Some anesthetists have used nitrous oxid from the start by simply allowing it to flow from a tube to the patient's nose and mouth, without any mask, and diminishing the quantity as cyanosis appeared. Crying children are easily and quickly anesthetized, and for this reason should not be given chloroform at all. Nitrous oxid, unless given by some open method, is a very poor anes- thetic for young children, as they do not seem to be equal to the task of breathing through valves. Ethyl chlorid is preferred by many anesthetists for young children. They usually succumb rapidly and without struggling or cyanosis. Infants should preferably be anesthetized in the mother's or nurse's arms. The method should be the same as for sleeping children.^ Care should be taken in anesthetizing children to make the operation as in- formal as possible. Mental suggestion here plays a great part, as well as gentleness in voice and movement. Questions such as "How old are you ?" or "What is your name ?" and immediately calling the child by the first name, put them at their ease at once. Avoidance of all appearance of restraint is necessary. Where a child is obstinate or terrified it is best to induce unconsciousness as rapidly as possible. Such children must be firmly restrained until this is accomplished. ^Latham A., and English, T. Crisp: "A System of Treatment," 3, 25. - See article on Alexander 's and Gwathmey 's ' ' Technique in Adenoid and Tonsil Operations. ' ' 328 ANESTHESIA Children Five to Eight or Ten Years of Age. — The anesthesia should be commenced with some perfume and continued by the drop method of chloroform or anesthol until the third stage is reached; then the second mask should take the place of the first and the anesthesia should be deepened and maintained by ether. This is the best method to use. English authorities recommend the C. E. mixture. The poison- ous effects of chloroform in connection with status lymphaticus need not be feared when chloroform is used in this way. Children under five years of age should not be kept under full surgical anesthesia more than two hours. Ten to Nineteen Years of Age. — The best anesthetic for young people is a Judicious combination of chloroform and ether given by the .vapor or drop method. No preliminary medication is usually necessary. In some cases, however, morphin and atropin, in small quantities, can be used to advantage to prevent excessive flow of mucus. One-twentieth to one-twelfth of a grain of sulphate of morphin, with 1/300 of a grain of atropin, is the usual dose. Nineteen to Fifty Years of Age. — Nitrous oxid and oxygen, the gas-ether, chloroform or anesthol-ether, or ethyl chlorid-ether sequences are probably the best agents for patients from 19 to 50 years of age. Preliminary medication for this class of patients must be considered as a part of the general anesthetic. It should be varied according to the size and condition of the patient. One-eighth to one-quarter of a grain of morphin, with 1/150 grain of atropin, can usually be given with very great advantage. Fifty and Over. — Elderly people yield more readily than do younger subjects to the combination of chloroform and ether by the vapor or drop method. The closed method or the gas-ether sequence is usually contraindicated. When atheromatous conditions are present, or cerebral hemorrhage from any cause is feared, ether is contraindicated, as is also nitrous oxid with oxygen. Chloroform with oxygen should be used in these cases. Weak, anemic men and middle-aged women yield better to nitrous oxid with oxygen, either alone or supplemented by small amounts of ether and chloroform. Many of these patients have some respiratory trouble, as chronic bronchitis or asthma, or arteriosclerosis. There is very little fear of chloroform poisoning in the aged, and yet it is always best to supplement chloroform by ether in sufficient quantity at least to maintain a good type of respiration throughout the anesthesia. Care should be taken to avoid the slightest cyanosis. Elderly patients are, as a rule, good sub- jects for anesthetization, not only in inducing and maintaining the anes- thesia, but also as regards after-effects. Heart Disease. — Unless some definite signs, such as swollen ankles, pulmonary edema, or dyspnea, are present, it is unnecessary to pay atten- ANESTHETIC AND TECHNIQUE FOR SPECIAL OPERATIONS 329 tion to any heart lesion. An open method is usually hest in these cases, anesthesia being induced with chloroform, the chloroform-ether mixture or anesthol, and continued with ether and oxygen. If loss of compensa- tion is present, as indicated by any of the above signs, pulmonary anes- thesia should be avoided and local or spinal anesthasia used. A preliini- nary dose of morphin may be used to advantage in these cases. A deep anesthesia is preferable to a light one. For paracentesis of the peri- cardium, nitrous oxid with oxygen is preferable. Pulmonary Tuberculosis. — Patients with tuberculosis should have nitrous oxid and oxygen Avhenever possible. Ether is contraindicated, as it is liable to light up a diseased lung that may have been in a quies- cent stage for some time. Warmed chloroform and oxygen is the second choice. Obese Patients. — As a general rule a healthy obese patient seems to be immune to any poisonous after-effects from chloroform. Obese pa- tients and those with obstructed or narrowed passages are best anes- thetized by warm chloroform and oxygen. Any closed method should be avoided with these patients. Thin Subjects. — With thin, anemic individuals all other anesthetics should be considered before using chloroform, anesthol, or ethyl chlorid. Athletes, Alcoholics, and Other Drug Habitues. — Athletes and per- sons addicted to the excessive use of alcoholic stimulants should always receive preliminary medication, regardless of the anesthetic selected. Morphin, with atropin or some other appropriate drugs, may be employed. For alcoholics, especially, if one to two ounces of whiskey in eight ounces of saline solution is administered per rectum, in combination with mor- phin given hypodermically, the anesthetic acts more satisfactorily than when alcohol is withheld. Persons addicted to the use of drugs, such as morphin, etc., should not be restricted before the anesthetic in the use of the particular drug concerned, biit should be given the dose to Avhich they are accustomed. The immediate ill results of withholding drugs at this time are easily recognizable, but the opportunity for its final dis- continuance is apparent. The requisite preliminary medication having been given, the vaj^or and drop method of anesthesia is preferable to any closed method, as these patients suffer especially from deprivation of oxygen. According to Mahoney,^ alcoholic subjects do better with treatment for a week or ten days with bromids, with the gradual withdrawal of alcohol. Treatment for even a few days is better than none. Diseases of the Lungs. — In pleurisy, empyema, abscess of the lung, and in all operations in which one lung is involved, the patient should lie with the diseased lung lower, in order to assist drainage and reduce ^ Mahoney, Daniel F. : "Some Considerations of Ether Anesthesia." Boston Med. and Surg. J., Oct. 19, 1911. 330 ANESTHESIA- the chance of infecting the healthy lung, and also to allow the healthy lung perfectly free respiratory action. If pneumonia is present and an operation is absolutely necessary, lo- cal, spinal, or rectal should be preferred before pulmonary anesthesia. In dyspnea' a, local, spinal, or rectal anesthesia is jDreferable to a pul- monary anesthetic. If, however, a pulmonary anesthetic is used, chloro- form with oxygen is the first choice, the patient being allowed to assume the attitude in which it is easiest for him to breathe. In acute or chronic bronchitis or phthisis, asthma, pneumonia or any diseases of the respiratory passages, ether is, if possible, to be avoided, even with the most improved methods of administration. Oxygen and chloroform or nitrous oxid and oxygen are the anesthetics to be chosen. Morphin or some similar medication should always be used . in these cases. Kidney Diseases. — In all kidney diseases ether and chloroform are usually contraindicated. Nitrous oxid with oxygen is the anesthetic to be preferred. In cases of diabetes in which sugar is either absent from the urine or present only to a slight degree, chloroform with oxygen anesthesia is unattended by risk, but when the quantity is abnormally large there is danger of diabetic coma. Chloroform should be avoided in these cases, and nitrous oxid and oxygen chosen as the anesthetic. These j)atients should be carefully dieted in order to reduce the amount of sugar to the minimum. Before regaining consciousness they may relapse into a coma- tose condition and die from acetonemia. (For a discussion of aceto- nemia, see Chapter IX.) Cancer. — Wherever the cachectic condition that is usually associated with advanced cancer exists, the patient takes kindly to the anesthetic and requires very little of it to maintain surgical anesthesia. These pa- tients should , always be given a preliminary dose of morphin before going to the operating table, as many of them have been accustomed to this medication. Eor removal of a cancerous breast, nitrous oxid and oxygen for elderly people, and ether and oxygen by the vapor method in younger subjects, are preferable, as the anesthetist is out of the way and shock is less liable to occur than with other procedures. Chloroform may be sparingly used in connection with the ether. It is best to antici- pate shock in these cases by giving one pint of saline with one ounce of glucose per rectum two hours before the operation. Fifteen to twenty miniites before any operation is concluded a pint of saline with three or four ounces of glucose should be given per rectum. Nervous Patients. — Nervous patients shoiild be gotten under the anesthetic as quickly as possible. The gas-ether sequence or nitrous oxid should be used. This prevents hysterical symptoms from appearing. Epileptics. — A preliminary of morphin is indicated for this special ANESTHETIC AND TECHNIQUE FOR SPECIAL OPERATIONS 331 class of patients and the anesthetic induced with chloroform, with a switch to ether in the second stage. The anesthetist must be ready to prop a mouth gag between the teeth if a seizure should occur as the patient is going under the anesthetic. The prop should be inserted be- tween the teeth as the patient is recovering. It is usually well to give a small hypodermic toward the close of the operation, as this will prevent a later seizure occurring. Insane Patients. — Insane patients should always Iiave a preliminary medication of morphin % of a grain one hour before the operation, to be repeated, with 1/150 grain of atropin, one-half hour before the anes- thetic is commenced. The anesthesia should be induced with chloroform . and maintained with ether and oxygen by the vapor method. Mental aberrations have been known to occur after the inhalation of any or all pulmonary anesthetics. This is probably caused by irregular or inter- mittent narcosis. Status Lymphaticus. — Definition. — Status lymphaticus or thymi- cus, or lymphatism, is a condition of infancy and childhood, marked by hyperplasia of the lymphatic structures, spleen and bone marrow, and persistence of the thymus gland (Stedman). It has also been defined as a condition of unstable equilibrium, coma, convulsions, and vomiting accompanying hyperplasia of the persisting thymus (Gould) ; and as a morbid state due to excessive production or growth of lymphoid tissues, such as the thymus and thyroid glands, resulting in impaired develop- ment, lowered vitality, and sometimes death (Borland). History. — As early as 1614 attention was called by Felix Plater to the fact that the thymus was enlarged in three cases of sudden death from dyspnea in one family. In 1823, and again in 1829, Kopp men- tioned the association of the enlargement of the thymus gland with sud- den death. Paltauf, in 1889 and 1890, collected, for the first time, a large number of cases of sudden death in adults, in which there was enlargement of the tonsils, lymphatic gland system, the follicles at the base of the tongue, the spleen, and the thymus gland, with narrowing of the aorta. Kundrat, in 1895, published ten cases of death immediately after anesthesia by chloroform or some mixture containing it, also one case in which ether was the anesthetic. Sudden deaths were noted after this time in many cases in which no anesthetics had been administered. Lymphatic hyperplasia has been found to occur in every chloroform fatality for the past twenty years in the children's clinic at Gratz. The first case recorded in England was reported by Wolff in 1905. Two deaths under local anesthesia have been recorded by Horoszkiewicz. Anatomy.^ — "The thymus gland is a temporary organ attaining its full size at the end of the second year, when it ceases to grow and re- mains practically stationary until puberty, at which period it rapidly ^Gray: "Anatomy/' 1442. 332 ANESTHESIA degenerates. It does not entirely disappear, for the shrunken and de- generate mass even in later life maintains a likeness to the original form and retains within its substance small portions of thymus tissue (Wal- deyer). If examined when its growth is most active, it will be found to consist of two lateral lobes placed in close contact along the middle line, situated partly in the superior mediastinum, partly in the neck, and ex- tending from the level of the fourth costal cartilage upward as high as the lower border of the thyroid gland. It is covered by the sternum and by the origins of the sternohyoid and sternothyroid muscles. Below, it rests upon the pericardium, being separated from the arch of the aorta and great vessels by a layer of fascia. In the neck, it lies on the front and sides of the trachea, behind the sternohyoid and sternothyroid muscles. The two lobes generally differ in size; they are usually con- nected so as to form a single mass but are sometimes separated by an immediate lobe. The thymus is of a pinkish gray color and is lobulated on its surfaces." Diagnosis. — The majority of writers are agreed that a positive diag- nosis of this condition during life is very difficult. The fact is that en- larged tonsils and the conditions termed status lymphaticus by most writers call for the extirpation of the tonsils with the idea of increasing oxygen in the tissues and the blood, and stimulating the growth of the individual. Connor ^ says : "The plainest sign of congenital hyperplasia of the vascular system is the noticeably small size and thin walls of all arteries." Pasty complexion, a large amount of subcutaneous fat, and, in adults, a scant amount of axillary or pubic hair are usual; also the hair of the head has a peculiar dry, brittle character. Enlargement of the faucial, pharyngeal, and laryngeal tonsils is frequently present. The diagnosis of a tumor running under the sternum would be almost pathog- nomonic of this condition. Cocks " considers the X-ray examination sec- ond only to the general condition of the patient in making a diagnosis. Most patients dying during or immediately after anesthesia have been young people or children, of flabby type, with enlarged adenoids, tonsils, thyroid (usually), and thymus; with narrow, high-arched palate, small mouth and throat, and weak heart sounds. During anesthesia a grayness of complexion or pallor is witnessed, with weak heart action and shallow breathing. Enlargement of the thyroid is said to exist in more than 50 per cent of cases. Enlargement of the tongue is an important factor in diagnosis. The spleen has been found to be greatly enlarged in many cases, also the mesenteric, popliteal, axillary, and inguinal glands. Exophthalmic goiter may also be present, in which event heart failure ^Connor: N. Y. State J. Med., 1906, 282-284. ^ Cocks : "A Contribution to the Pathology and Clinical Diagnosis of Status Lymphaticus," read before the Am. Laryn., Rhinol., and Otol. Soc, May, 1912. ANESTHETIC AND TECHNIQUE FOR SFKCIAL OPERATIONS 333 under the anesthetic is probable. Congenital defects such as cIciFt palate and cleft kidney are sometimes associated with status lympliaticns. All patients have a pale, thin skin, pasty complexion, and usually subcu- taneous fat. The glands of the neck are also sometimes enlarged. The above complex symptoms are noted when, given chloroform for any length, of time, much of the anesthetic is absorbed and less secreted than is usual, with a consequent continual poisoning of the system until death occurs several days after the anesthetic. Sometimes delayed chloroform poisoning is mistaken for status lymphaticus. In status lymphaticus, especially in children, patients seem to dread the anesthetic more than is usually the case. This fear would certainly add to the shock and decrease the normal resisting force of all the organs to the effects of the anesthetic. Two cases of death, noted by Wheelock,^ at Fort Wayne, were due to cardiac failure and asphyxiation. In cardiac failure no premonitory symptoms are present, but in asphyxiation there is a disturbance of breathing at various times. An enlarged thymus has sometimes produced pressure 'from which asphyxial symptoms have de- veloped. In some of the reported cases, death occurring during anes- thesia always came suddenly, with pallor and dilated pupils. In some there were superficial respiration and intermittent pulse just before the last signs mentioned, together with cyanosis and dyspnea. Ohlmacher ^ states that deaths from status lymphaticus are due to increased intra- cranial pressure, with sudden edema. Halstead ^ points out the great danger of operating for adenoids and tonsils upon children with status lymphaticus, on account of the great shock which the added fright and violent struggling would bring on — in some cases- enough to produce death. Choice of the Anesthetic for Suspected Cases. — From the study of a large number of statistics, the fact that chloroform is contraindi- cated cannot be questioned. Eoberts ^ concludes that ether is the safest anesthetic for all of these cases. Unquestionably chloroform should be avoided in all suspected cases. Ether by the vapor or drop method should be the anesthetic of choice. Ko closed method should be used on account of the possibility of pressure symptoms. Children who sink into deep anesthesia quickly from small doses of the drug should at once be considered questionable cases for the anesthetist. Peepaeation for Operation. — Great precaution should be taken that the preparation and preliminary medication be complete, so that whatever is given, when the time for operation arrives, the patient will be in a more or less drowsy condition and indifferent to the anes- 1 Toledo Med. and Surg. Sep., 1909, 35, 395-399. 2 J. Am. Med. Assn., Feb., 1904, 4S, No. 7. sPhila. Med. J., Nov. 3, 1900. 4 Trans. Am. Laryn., Eliinol. and Otol. Sac, St. Louis, 1908, 507-524. 334 ANESTHESIA thetic. (See Chapter IX, Treatment^ Preliminary, Dwing, and After Anesthesia, p. 365; also Acetonemia. Treatment During Anesthesia, — If sudden syncope occurs, mas- sage of the heart, in connection with artificial respiration, should be insti- tuted immediately. Hilliard ^ thinks that the hypodermic injection of morphin and atropin before the administration of the anesthetic is of great value, and that, with this addition, general anesthesia is safer than local anesthesia. Fig. 131. -The Gwathmey Three-Bottle Vapor Inhaler, Mouth Gag, with Hollow Tubes Attached. (See page 323.) Mortality. — Harvey Hilliard ^ gives a very complete history of a fatal case of status lymphaticus in a young man aged twenty-one, six feet two inches in height, very thin, and of a highly neurotic temperament. Operation : circumcision. The patient was a great smoker of cigarettes and subject to attacks of faintness. The patient had the usual preparation, but was allowed to smoke during the morning, the operation being at twelve o'clock. Hil- liard found on examination a rapid pulse, poor chest expansion, and con- siderable enlargement of the thyroid gland. Chloroform-ether mixture was the anesthetic. During the induction period, the heart beat very vio- lently. A light anesthesia was maintained. When the prepuce was severed, the patient turned an ashen color and stopped breathing. Khyth- mic tongue traction was employed and amyl nitrite vapor, the adminis- trator pressing the lower ribs to restore respiration. This brought the patient round. The anesthetic was discontinued with the idea of dis- continuing the operation, when the patient immediately stopped breath- ing. The usual restorative methods were resorted to, but proved unavail- ing. Artificial respiration was kept up for forty-five minutes, but the patient did not again come around. 1 Hilliard, Harvey : "A Fatal Case of Status Lymphaticus, ' ' Brit, Med. J., Jan. 25, 1908, 202. 2 Idem : Loc. cit. ANESTHETIC AND TECHNIQUE FOR SPECIAL OPERATIONS 335 Post-mortem examination sliowed the thyroid gland enlarged, with degenerated changes. The thymus gland was persistent and weighed 24 grams. The heart was dilated, with thin, flahby walls. In thirty-five cases reported by McCardie the average age was six- teen years, the youngest patient being six months ; seven were under ten years of age, fourteen between the ages of ten and twenty, eight from twenty to thirty, and two from thirty-one to thirty-two, the oldest being fifty-five years. There was no distinction as regards sex. Cocks ^ reports forty-six cases of status lymphaticus in approximately sixteen hundred autopsies at the Bellevue Hospital Pathological Depart- ment. In thirty cases examined by McCardie for status lymphaticus the deaths during or after anesthesia were: seventeen from chloroform, six from ether, five from a mixture of chloroform and ether, and two doubt- ful cases, in which the anesthetic was nitrous oxid. There is also re- corded the death of an infant, one year old, after an injection of 1/13 of a grain of morphin, in whom post-mortem examination revealed the signs of status lymphaticus. Two deaths are reported under local anes- thesia, both patients being women, aged thirty and thirty-one years, respectively. Death from any cause, and especially during the anesthesia, is always very sudden. In rare instances the enlarged thymus gland may com- press the trachea sufficiently to cause death by suffocation. Toxemia in- duced by the thymus may reduce the subject to such a degree that sud- den shock may cause death, toxemia being primarily responsible. Pa- tients have also been known to die from such a trivial shock as bathing. PosT-MoRTEM Examination. — Autopsy usually showed adenoids and tonsils enlarged, thymus gland very large, and spleen also enlarged; heart and liver healthy. The aorta and small arteries were smaller and thinner than normal, with signs of cardiac dilatation, evidence of recent rickets, and sometimes incomplete development of the sexual organs. In some cases fatty degeneration of liver (principally), kidneys, heart and other muscles was noted. Hyperplasia of the lymphatic glands is usually noted, also evidence of infantilism, such as, for example, scanty pubic or axillary hair. Exophthalmic goiter is frequently associated with status lymphaticus. Cocks reports over fifteen deaths occurring in connection with cerebrospinal meningitis. Observation Upon Animals. — Oifergeld and Miiller ^ have made a number of interesting experimental narcoses upon animals with the following results (presumably with chloroform at room temperature in all cases and without oxygen except as stated) : * Cocks: Loc. cit. - Offergeld and Miiller : ' ' Experinienteller Beitrag z. toxischen Wirkung des Chloroforms auf die Nieren," Arch. f. Min. CUr., 1905, 75, 758. 336 ANESTHESIA Animals chloroformed for two hours, after recovery from the immedi- ate effects of the anesthetic, usually died from 48 to 60 hours afterward; post-mortem examination showing parenchymatous degeneration of the heart, liver, and kidneys. When artificial nephritis was produced, exten- sive injury occurred even with a fifteen-minute anesthesia. When injured by mineral acid, pus, germs, or the injection of diphtheria toxins, it was found that the kidneys were usually affected by chloroform narcosis. When pregnant animals were used, this fact in itself did not favor fatty degeneration unless complicated with kidney lesions. A second chlorq- formization favored greatly the degenerated changes in the kidneys. Fat seemed to disappear in the tissues and to accumulate in the liver. Offer- geld concluded that anemic and cachectic conditions of the patient fa- vored the poisonous action of chloroform, and he warned against the danger of repeated chloroform anesthesias. He also Relieved that the prevention of the ill effects of chloroform might he accomplished by a mixture of chloroform and oxygen. ]\Iiiller concluded that the changes in the internal organs always appeared first as fatty changes, depending upon the time and number of the anesthesias ; that these changes were in direct proportion to the anes- thetic power of the agent used ; that they usually disappeared after anes- thesia; that a second anesthesia was always very dangerous; that the fatty changes following the second anesthesia were twice as severe as from the first, regardless of the time given; that the second anesthesia should never be given for at least three days after the first; that pneu- monias occurred frequently with ether; that chloroform should be the second anesthetic; that mixed anesthesias did not prevent these fatty changes; and that these changes took place in the vessel walls of the brain as well as of the other internal organs. Bandler's ^ experiments seem to show that ether does not produce the changes in the liver cells caused by chloroform. Strassmann ^ chloroformed animals previously weakened Ijy loss of blood, with a greater resulting fatty degeneration than upon normal ani- mals. The senior author (J. T. G.) agrees with Henderson " that unskillful anesthesia is more often the cause of death, and especially in adenoid and tonsil cases, than the status lymphaticus or heart disease. Henderson states that "writers assume that status lymphaticus was the cause of death, although there may have been no autopsy. Even in those cases in which an autopsy was performed, the pathologist's report sometimes ^ ' ' Ueber den Einfluss der Chloroform und Aethernarkose auf die Lieber, ' ' Mittlg. aus den Grenzgeieit. der Med., 1896, 1, 30.3. ""VircTiow's Arch., 1899, 115, 1. ^Henderson, Yandell: "Primary Heart Failure in Normal Subjects Under Ether," Surg. Gyn. and Obstet., Aug., 1911. ■'' ANESTHETIC AND TECHNIQUE FOR SPECIAL Oi'ERATIONS 337 indicates that if he had not been told what to' find he wo uhl scarcely have found it. "On looking up the general subject of status lyraphaticus, I find that this mysterious (I might almost say mystical) condition was only a few years ago used in precisely the same way, and with the same confidence, to explain another class of fatalities. It is less than a decade since the time when, if a patient died suddenly after an injection of antitoxic serum, an unsuspected condition of status lymphaticus was invoked as the explanation. In many of the very best text-books of pharmacolog)' (written, by the way, by laboratory men), the practice of occasionally interrupting the administration of ether, and of allowing the patient to come for a few moments pretty well out of anesthesia, is expressly recom- mended. If anesthetists will only realize that this is a procedure which, above all others, should be shunned, the number of cases of so-called status lymphaticus fatalities, under anesthesia, will, I believe, show a sudden and marked decrease." Henderson concludes his article by stating that "unsuspected cases of status lymphaticus are often invoked after tonsil operations, which are due entirely to the ether being administered intermittently and the sub- ject rapidly coming part way out of the anesthesia rather than to any connection of the tonsils with the thymus." SPECIAL OPERATIONS Short Operations. — Precautions. — As many fatalities have been re- ported from all anesthetics for short operations, it is well to state the means of avoiding them or reducing them to the minimum in the fu- ture. First: With the exception of emergency cases, all patients should be as well prepared for a minor operation as for a major one. Second: Eules regarding diet, cleansing of the gastro-intestinal tract, and also preliminary medication, if the psychic element is in evi- dence or much suffering is anticipated after the operation, must not be neglected. Third: Constrictions around the neck and waist, such as a tight collar band, corsets, or belts, should be removed. Fourth : The head and trunk should be in one straight line and the anesthetic given as speedily as consistent with safety. Eegardless of the anesthetic used, all bandages around the abdomen or neck should be cut, but not necessarily removed. It is impossible to induce a smooth anesthesia with bandages in place. In all operations upon the head, neck, or upper air passages the anesthesia must be con- siderably lessened before the bandages are reapplied, otherwise cyanosis 338 ANESTHESIA may appear and the patient will remain under the anesthetic an unneces- sarily long time. When the sitting or semi-sitting position is used, chloroform must not be given. Nitrous Oxid. — For all short operations nitrous oxid, first through valves and then with to-and-fro breathing until deep anesthesia ensues, is the best method. Hasbrouck,^ of New York City, who has given nitrous oxid for the extraction of teeth over 100,000 times, prefers nitrous oxid alone, and administers oxygen only as indicated. From his large experience he declares that while patients suifer little nausea or vomiting from the combination of oxygen with nitrous oxid, a still smaller percentage have any after-effects with the nitrous oxid alone. No one is justified in giving nitrous oxid without having ianhs of oxygen in place and available for immediate use. Nitrous oxid is the recognized anesthetic for the extraction of teeth. It should also be used for dislocations, opening abscesses, breaking up adhesions, examinations, removing or reapplying painful dressings, etc. For prolonged dental work the nasal inhaler should be used and a combination of nitrous oxid and oxygen under pressure given. Nitrous oxid and oxygen may be used for its analgesic quality, the patient never reaching the anesthetic stage. Exceptions to the above rule for selecting nitrous oxid or nitrous oxid and oxygen for short operations is where there is any great swelling or engorgement of the neck. The administration of gas in this condi- tion may quickly induce dangerous symptoms. The author knows of one case in which a fatality occurred when nitrous oxid and oxygen were given for the extraction of a tooth. An undetected abscess at the base of the tongue burst at the height of anesthesia and immediately filled the patient's lungs with pus, the patient dying within three minutes. Ethyl Chlorid. — Ethyl chlorid is contraindicated for extraction of teeth unless oxygen is used with it or nitrous oxid is not available, not only on account of the possibility of a fatality, but also because of the nausea and dizziness that so often follow a short application of this anes- thetic, the percentage of cases nauseated being much greater than when nitrous oxid or nitrous oxid and oxygen are used. Chloroform and Ether. — Chloroform is contraindicated, as there is a very great possibility of a fatality unless a deep anesthesia is main- tained. There is no contraindication to ether except for the after-effects. In ophthalmic cases, in which quiet is absolutely essential, chloroform by the vapor method, and with oxygen, is preferable to any other com- bination. This applies especially to such operations as iridectomies. Nitrous oxid with air or oxygen is contraindicated in these cases on account of increased congestion of the blood vessels, as is also any closed method. For enucleations a preliminary medication is indicated, and ^Personal communication. ANESTHETIC AND TECHNIQUE FOR SPECIAL OPERATIONS 339 some closed method preferably should be used to initiate the anesthetic. The narcosis should be continued with some form of vapor anesthesia. Chloroform should be avoided if possible at this time. It is unnecessary now, as formerly, to anesthetize deeply with ether and depend upon the resulting anesthesia for the operation. Paracentesis of the membrana tympani should only be done under nitrous oxid with oxygen (preferably) or nitrous oxid alone. Ethyl chlorid would be the third choice. The Mastoid. — Of all serious surgical cases the easiest, from the anesthetic standpoint, is a mastoid operation. A deep anesthesia is re- quired only in the initial stages. The hammering and chiseling seem to have some anesthetic effect, as the vapors can be almost withdrawn and the reflexes allowed to become quite active without the patient evin- cing any conscious movement. If nausea follows a mastoid operation, the anesthetist has not measured up to his opportunities. Generally speaking, the best procedure for mastoid cases is to begin the anesthetic by the drop method of chloroform, gradually switching to the drop method of ether and then changing to the oxygen-ether vapor method. This gets the anesthetist completely out of the way and the patient comes out of this anesthetic, as a rule, without any nausea, vomit- ing, or shock. The nitrous oxid-ether sequence or any closed method is contra- indicated, as the bag and mask are more or less in the surgeon's and assistant's way. Preliminary medication of morphin or something simi- lar is most helpful in these cases. The Tipper Respiratory Tract. — In all operations upon this part of the body a preliminary douching with some antiseptic (in some in- stances to clear the parts of the blood and pus) is absolutely essential. As a general rule, any closed method should be avoided with this special class of operations. Chloroform for the induction, and chloro- form and oxygen, or ether and air, for the maintenance, is the best procedure. Excision of the Tongue. — The majority of surgeons seem to prefer the dorsal position for excision of the tongue, with a sandbag under the shoulders, or with the headpiece slightly dropped. In this position, when the head is well flexed and the anesthetist supports the lower jaw with one hand, a clear airway is easily maintained, the blood and other secre- tions being more easily removed than by any other method, and, conse- quently, with less discomfort to the patient afterward. Some surgeons prefer the upright position. The anesthesia can be easily maintained by means of this vapor method, with the tube ending in the mouth or nose, or pharyngeal or intratracheal insufflation. Pharyngeal anes- thesia (see p. 335) is, as a rule, all-sufficient. For excision of the glands of the neck or operations upon the lips 340 ANESTHESIA and cheeks some form of vapor anesthesia should be employed. In all of these eases a deep anesthesia is best, unless facilities for removing blood are not adequate when the patient's cough reflex is allowed to re- main. ' Cleft Palate. — It is well to avoid gas as the initiatory anesthetic for these operations, anesthol or chloroform being the best. The anesthesia can be maintained by ether with oxygen or air and by the vapor method. In intranasal and antrum of Highmore operations the anesthesia should be maintained by the vapor method. Submucous Operations. — While the majority of j^hysicians do these operations in their offices under some local anesthetic, lately it has been urged that these can be better operated upon under a general anesthetic. Closed methods should be avoided, and the anesthetic should usually be induced with chloroform and maintained with chloroform and ether by a tube in the mouth. The patient should always have some preliminary medication. Adenoid and Tonsil Cases.- — In adenoid and tonsil cases, to-and-fro breathing of nitrous oxid followed immediately by ether, and supple- mented later by the vapor of ether passed through a tube placed either in the mouth or nostrils, is the best. In all operations upon adults, where the mouth must be open, as the excision of the tongue, jaw, etc., the vapor method should be used, preceded by the drop method of chlo- roform and ether, or the nitrous oxid-ether sequence, according to the patient. The exception to this rule will be where the patient has some lung trouble. In that instance, rectal or morphin anesthesia, or spinal analgesia, should be used. Alexander's- ^and .Gwathmey's technique ^ in adenoid and tonsil opera- tions covers the ground for the operations in the recumbent position. We quote voluminously from this paper. The ideals for which one should strive may be divided as follows: 1, preparation of patient; 2, good anesthesia ; 3, good technique ; and, 4, after-treatment. Preparation of Patient. — The night previous to the operation the patient is given a cathartic; to adults, some cathartic pill; to children, castor oil or calomeL The next morning, if the result is not satisfac- tory, a simple enema should be given, at least two hours before the opera- tion. The temperature is then taken. 'No food is allowed for six hours before the time of operation. If the operation is early in the morning, no food whatever should be given. The last meal should consist of a plate of clear soup or bouillon with two crackers. Cases are on record of children vomiting a bolus of food or a small piece of undigested meat, which, getting into the trachea, caused serious disturbances, even septic pneumonia. Milk is especially prohibited. From nervousness or other ^"Technique in Adenoid and Tonsil Operations," N. ¥. Med. J., March 11, 1911. ANESTHETIC AND TECHNIQUE FOR SPECIAL OPERATIONS 341 causes this coagulates, and the vomited curds are as much of a menace as particles of any other article of food. For nervous children over six years of age, chloretone, five grains, given one hour before operation, is valuable. From fifteen years up- ward, one-eighth or one-sixteenth grain of morphin, and one one-hun- dredth-and-fiftieth grain of atropin should be given, or ten grains of chloretone one hour before operation. Immediately before the operation, the upper air passages should be sprayed with some antiseptic solution. Liquid petrolatum with men- thol is especially recommended, as it lubricates the passages, facilitating the passing of the catheters. This procedure has quite a psychic effect, in addition to the physical, that is most beneficial. In addition to the preliminary treatment, mental suggestion is here of the utmost importance, and varies with the characteristics of difl^erent patients. On the table, the j)atient wears a loose, warm gown or robe, thick woolen socks, and is covered by a blanket, over which is placed a rubber sheet, fitting closely around the neck. Care should be taken to prevent any constriction at the neck or waist. The hair is covered with a sterile towel, as is also the rubber sheet. Anesthesia. — The ideal anesthetic for this particular operation must be safe; deep enough to abolish all reflexes, including the cough, swallowing, and tongue reflexes; and continuous, so that there will be no necessity for the reapplication of the anesthetic or for the delay caused lay the removal of blood from the operative field. Furthermore, the pa- tient should come out of the anesthetic within fifteen minutes, in a natu- ral way, without delirium or nausea. Vomiting is reduced to a mini- mum if no blood is allowed to enter the stomach during the operation. For a very nervous, child, or one having experienced previous fright from any cause, the time of operation should be in the early morning, say, one hour before the usual time for the child to awaken, or during the noonday nap. The patient should be anesthetized while asleep. This has been done many hundreds of times, and with children is much safer than any other method. To successfully anesthetize a sleeping child, the mask or gauze should never touch the face. The anesthetic is begun with chloroform, a few drops at a time, and gradually increased until rhythmical and automatic respiration indicates the commencement of surgical anes- thesia. A change to ether by the vapor or drop method is then made. On account of the undeveloped muscles of children under six years of age, these patients should be anesthetized by the vapor or drop method of ether or chloroform. Any closed method puts too severe a strain upon the chest walls. The usual procedure is as follows: In all cases in which the drop or vapor method is used, a few drops 342 ANESTHESIA of cologne upon the mask, just before the anesthetic is started, will allay fear, and increase confidence in the anesthetist. From three to six drops of chloroform are then given, followed by as many of ether, then alternat- ing, and changing entirely to ether as surgical anesthesia is reached. This procedure gets the patient under the anesthetic in from three to five minutes, and without any struggling. One should always bear in mind that many of these little patients have the lymphatic temperament, in which chloroform is absolutely contraindieated. Whenever this is suspected, the drop method of ether, given carefully and slowly at first, and increased rapidly as the stage of surgical anesthesia approaches, will bridge over the disagreeable features which sometimes occur with this method of anesthesia. From six years of age upward, decidedly the best technique is the gas-ether sequence, followed by the vapor method. The ether or chloro- form is passed through a tube attached to the mouth gag. If a patient has bronchitis or a catarrhal condition of the upper air passages, ether is absolutely contraindieated. Warm chloroform and oxygen is the safest anesthetic for this condition. .The tube on the suction apparatus in the mouth, as employed in a large number of cases, has been found to be more or less in the way, and, to obviate this, we have adopted the plan of placing the catheters at- tached to the suction apparatus in the nares, so that the ends are just visible when the tongue is depressed. This compels the patient to breathe through the mouth, and the anesthesia is more easily maintained in this way than by any other method. (Fig. 93.) The patient thus receives all the vapor, and the blood is not in the way of the operator. Surgical anesthesia is as easily maintained in this way with ether as with chloroform. Hewitt uses the gas-ether-chloroform sequence for this operation, as do also others who make a specialty of anesthetizing for nose and throat operations. With the bent tube in the ether chamber we are enabled to get a more nearly saturated ether vapor than ever before, thereby rendering the use of the chloroform unnecessary in a large majority of cases. This method seemed to work well in one or two cases, but was not a complete success, so we finally abandoned it and developed the present method. So far, the nasal tubes have acted perfectly in taking up the blood, and no trouble is experienced in keeping a clear field for the operator. A tube was formerly attached to the tongue depressor, but it was found that the tongue depressor had to be removed occasionally, during which time the patient might regain the lost reflexes and thus cause the sur- geon embarrassment. With the vapor apparatus as now perfected, we are able to give a continuous anesthesia after the mouth gag has been placed ANESTHETIC AND TECHNIQUE FOR SPECIAL OPERATIONS 343 in position, and the patient is in any posture desired by the surgeon. If the operator prefers the patient in a dorsal position, it is unneces- sary to turn the head to either the right or left, to stop the operation for the reapplication of the anesthetic mask, or to re- move the blood from the oral or nasal cavities. By means of this con- tinuous narcosis, together Avith the use of the blood suction apparatus, the time of operation is re- duced from one-third to one-half. The surgeon is also enabled to do more thorough work, without the feeling of the neces- sity of hurrying lest the patient come out of the anesthetic, since as even a plane of anesthesia can thus be maintained as for any other surgical pro- cedure. Deep chloroform nar- cosis, with great profusion of hlood in this position, is more or less dangerous. For this reason the gas- ether sequence to get the patient deeply under the influence, followed hy ether vapor anesthesia, is nearly ideal for this par- ticular operation. When ether is contraindicated, a tube from the oxygen tank replaces the foot pump. Warm oxygen alone, or oxygen with chloroform, may thus be given as indicated (Fig. 107). Suction Apparatus. — This consists of a vacuum water pump (Fig. 133), which is attached to any spigot or tap by an adjustable connec- tion (Fig. 133). The rush of water through this brass cylinder creates a diminished pressure which is transmitted to a Wolff bottle by connect- ing rubber hose. Another rubber hose leads from the Wolff bottle to Fig. 132. — The Watek Suction Apparatus foe Adenoid and Tonsil Operations. 344 ANESTHESIA the patient; to the free end of this hose are attached two rubber cathe- ters, which, when placed in position, utilize the vacuum and complete the apparatus. Good Technique. — The desiderata in the matter of good technique are : 1, Good light ; 2, bloodless field ; and, 3, maximum speed. Good Light. — After experimenting with various forms of reflected light, we find direct illumination of the operative field to be the most Fig. 133. — Pump Attached to Spigot With Water Turned On. desirable. This is obtained by using an electric headlight and condenser, supplied by a dry cell battery, or, better, by a current controller. Shielded lights on instrument and anesthetic tables prevent interference with the operator's light. By means of the brilliantly illuminated field so provided, anomalies of formation are noted, and bleeding vessels may be seen and clamped, thereby avoiding much tissue laceration and bleeding. Bloodless Field. — Our attempts at reaching this ideal are still in the formative period; so much has already been gained, however, that we feel justified in reporting the method. Our efl:orts were addressed to, firstly, the reducing of the blood lost ; and, secondly, to the removal of ANESTHETIC AND TECHNIQUE FOR SPECIAL OPERATIONS 345 that which was lost. We attempted, as detailed under anesthesia, to de- crease by sequestration the amount of blood volume in the operative area. Our experiments to date have convinced us that this procedure, when perfected, may be of positive value. Immediately after the enucleation, a pad of gauze, firmly pressed into the bleeding area, helps to reduce tlie hemorrhage ; however, the sum total of blood lost was not much affected, until, after much experimenting, we evolved the present method of blood removal. This consists of a graduated AYolff bottle, suction pump, and attachments. Eubber catheters, with several additional holes made near their tips, are introduced through the nares as soon as surgical anesthesia is pres- ent. They are allowed to lie alongside of each other in the pharynx, their ends about an inch above the epiglottis. The enlarged ends of the catheters are joined by a Y connection with the rest of the apparatus, the tube passing over the patient's head. With the patient's head thrown back, this region becomes a natural reservoir, which is thus readily drained. As soon as we began using this method, we noticed a marked reduc- tion in the amount of blood and mucus collected. Previous to using the catheters, our average of many cases was four ounces; now it is seldom over two. A study of the blood supply of the tonsillar area throws no light on the reason for the diminished hemorrhage, yet it has occurred in too many cases to be a coincidence. After complete removal of adenoids and tonsils, the patient is turned on one side, the catheters are withdrawn, and the vault is explored with the finger for shreds. The vault is now wiped over with alcohol on gauze, and the nares are douched with cold saline solution. This latter procedure washes out all clotted blood, and hastens the patient's return to consciousness. Maximum Speed. — Maximum speed is obtained by simplicity of method in operating. A skilled anesthetist and an assistant physician or nurse are essential. An occasional swab is employed to remove clotted blood not sucked up by the catheters. The adenoids are then removed in the usual way. The average time of operation is eight minutes. After-treatment. — The patients are kept in bed for twenty-four hours, and given liquid food. The throat is sprayed every two hours with mild liquid antiseptics and a hydrogen peroxid solution, used alter- nately. When cervical stiffness is present, massage and hot applications are employed. Complications are met with appropriate remedies. The Upright Position. — Many operators prefer the upright posi- tion for adenoid and tonsil operations. French,^ of Brooklyn, has de- vised a chair table, and has worked out a technique that approaches the ideal for operations in this position. "The method consists in placing . ^Trench, Thomas E.: N, Y. Med. J., June 1, 1912, 1125. 346 ANESTHESIA the patient upon a table for anesthetization in the recumbent position, and, when tlie stage of excitement has passed, in converting tlie table into Fig. 134a. — Dr. French's Chair Table. a chair and bringing the body to the sitting posture ; or, for that matter, placing it in almost any position except one with the face downward. (See Figs. 134a to 134 j.) Fig. 134b. — Dr. French's Chair Table. "Before the patient is wrapped in a blaiiket, a stout, four-inch bandage is made to encircle the upper part of the back, the ends being ANESTHETIC AND TECHNIQUE FOR SPECIAL OPERATIONS 347 drawn up under the axillae and over the front of the shoulders, and for the moment allowed to hang in the recesses on either side of the head Fig. 134c. — Dr. French's Chair Table. rest (Fig. 134 B). After the patient has been wrapped in a blanket, the leather straps attached to the seat are fastened rather loosely around the hips, and the legs, below the knees, are strapped to the footrest (also shown in Fig. 134 C). When the patient is nearly anesthetized Fig. 134d. — Dr. French's Chair Table. the anesthetist turns the wheel at the junction of the back of the chair with the seat, and the body is thus raised sloAvly forward (Fig. 134 D) to 348 ANESTHESIA the upright position, the mechanism being so constructed that as the back ascends the footrest descends. The seat, which is a trifle higher in front than at the back, is covered with a mat of corrugated rubber, which checks largely, if not entirely, the tendency of the body to slide toward the foot of the table or chair. While the upward movement is taking place, the headrest is adjusted to the patient's head by means of Fig. 134e. — Dr. French's Chair Table. the smaller wheel on the side of the back section (Fig. 134 E), and this is accomplished with such ease and accuracy that the position of the head for the proper administration of the anesthetic and the desired dis- play of the field of operation can be readily maintained. At the same time the shoulder bandage is adjusted by drawing the ends around the headrest, when they are caught under, and tied to a hook on the back of the chair. The patient has now reached the upright position and is ready for operation. If the surgeon desires to operate while standing, the chair part of the mechanism can be raised (by means of the large wheel ANESTHETIC AND TECHNIQUE FOR SPECIAL OPERATIONS 349 in the frame of the base) sufficiently to bring the head of the patient opposite his own (Fig. 134 F). If, however, he desires to operate while sitting, the chair can be lowered, if necessary, as far as the base (Fig. 134 G), and these movements can be made with surprising ease, even if the patient's body is of great weight. Figure 134 G also shows the anesthptist standing inside the rear part of the frame of the base, in Fig. 134f. — Dh. French's Chair Table. which position he can administer the anesthetic and control the mechan- ism of the chair. If respiratory troubles arise, and it is desired to lower the patient's head, this can be quickly done by tilting the chair backward (Fig. 134 H), and then by wheel action converting the chair into a table top in the Trendelenburg position (Figs. 134 I and 134 J). "With an ordinary chair, or even with the special chair as previously constructed, it has been, at times, very difficult to place and keep the head of the patient in the required position for the proper administra- tion of the anesthetic and for easy access to the field of operation. With the new method, the inexperienced interne or newly graduated medical Fig. 134g. — Dr. French's Chair Table. Fig. 134h. — Dr. French's Chair Table. ANESTHETIC AND TECIiNIQUE FOR SPECIAL OPERATIONS 351 Fig. 134r. — Dr. Fbench's Chair Table. man can, under instruction, bring the patient to, and maintain him in, the upright position, with perfect ease and safety. This is accomplished partly by means of wheel devices, the slightest turn of which either raises or lowers the upper portion or the whole of the body, or elevates or de- FiG. 134j. — Dr. French's Chair TABiiE. 352 ANESTHESIA presses the headrest, and that, too, without further need of attention than is required in turning them. ''The secret of a safe and an uninterrupted administration of an anestlietic in the upright position is in keeping the neclv somewhat stretched and the head moderately extended over the headrest." French states that "a sudden change from the horizontal to the up- right position, while the patient is under ether narcosis, is apt to occa- sion a too rapid development of cerebral anemia and a consequent loss of cardiac balance. "Experience would seem to show that the danger of blood flowing into the trachea is no greater during the routine operations which we are wont to perform in the nose and throat when the body is upright than when in the Eose position. "The blood thus flowing into the gastro-intestinal tract has never, in our experience, made its presence manifest by untoward disturbances in that canal. Our results, in the considerable number of patients upon whom we have operated in the upright position, have led us to the con- viction that the fear of blood flowing into the air passages is based upon theory and not upon fact. "There is less shock, and less disturbance in other ways, to the pa- tient after operation because less ether is required to maintain narcosis when the sitting posture has been attained. This is, no doubt, due to the diminished blood pressure in the vessels of the head when the body is in the upright position and under the influence of a general anesthetic. The difference between the flushed face in the recumbent position and its relatively pale appearance in the upright position is at times very marked. The difference in the quantity of the anesthetic required is, we believe, due to the difference in the amount of blood in the brain in the two positions, which, in French's opinion, is another reason for this special technique. "The abstraction of a considerable quantity of blood from an anemic child adds to the cachexia, diminishes its rallying powers, and reduces the body resistance in the event of the onset of any special disorder. Shock is felt more by the child than the adult, and although the child recovers from the shock more rapidly the ultimate recovery will be re- tarded if a considerable amount of blood has been lost. As a rule, chil- dren in a fair state of health before operation sustain the loss of a rela- tively large quantity of blood in a very remarkable way, and in time recover their usual, if not better, health, but they do not always do so without concurrent disturbances; and how often such disturbances are due directly or indirectly to the loss of blood it may be difficult to say." For operations upon the tonsils and adenoids under nitrous oxid and oxygen, see page 156. Tracheotomy. — It is sometimes safer to perform this operation under ANESTHETIC AND TECHNIQUE FOR SPECIAL OPERATIONS 353 a local anesthetic on account of the congestion produced or difficulty in breathing if a general anesthetic is used. When there is no obstruction in any part of the air passages, there is no objection to doing a trache- otomy under general anesthesia. After the tracheal tube is inserted, anest"hesia is easily maintained by chloroform or ether vapor. If no vapor apparatus is convenient, an ordinary mask is held over the trachea, and the anesthetic carefully given. For thyroidectomies careful pre- liminary medication is essential, and the anesthcJtic should be instituted very slowly and carefully. Chloroform and oxygen is probably the best anesthetic to use. Any closed method is contraindicated, as there is always the possibility of the thyroid lessening the diameters of the air passages by pressure. Goiter (Angina Lndovici, Exophthalmos — Graves' Disease). — If a general anesthetic is determined upon, ether and chloroform with oxygen by a tube is probably the best method of administration. Closed methods should be avoided with these cases, as deaths have been reported under nitrous oxid and ethyl chlorid. Many surgeons prefer a local anesthetic. (See page XIV.) Crile's method of "stealing upon the thyroid" has been widely adopted. He states: "In cases of Graves' disease the mere proposal to perform an opera- tion becomes also a pathological excitation; this excitation may so much increase the disease that the patient is even less able than before to bring herself to submit to adequate treatment. On all sides this disease is beset by vicious circles; by pathological interactions. The ideal plan of approach, at least in my experience, is to assure the patient that hers is a curable malady, that it can be treated in a hospital, and that non- operative measures will first be tried; then if they prove inadequate a simple operation will be done; that it will be best to leave this decision to the judgment of her medical adviser, and that, since even the discus- sion of operation is both unpleasant and injurious, it would be best not to open this subject again. The patient usually gladly consents to leave the whole matter to the judgment of the physician, and the way is then opened for the most effective treatment which in my judgment has ever been proposed — namely, ligation or excision on the new principle of anoci-association." The technique is as follows : "For about five days before the opera- tion the patient is treated every morning. A hypodermic injection of sterile water and inhalation of fresh air with a little nitrous oxid through the same inhaler that will be used on the day of operation is what constitutes the treatment. The entire treatment lasts five minutes each day. The tachycardia and other nervous symptoms that usually occur with each treatment become less marked as the day of operation approaches. On the morning of the operation, which is performed in 354 ANESTHESIA one of the favorable phases of the numerous cycles of the disease, the patient receives the treatment as usual. One-eighth to one-sixth of a grain of morphin and scopolamin (atropin should be omitted in these cases) is substituted for the sterile water, and the nitrous oxid is carried to the stage of surgical anesthesia. The patient falls asleep in her bed without realizing that the first step of an operation has already begun. The patient is then transported anesthetized to the operating room, where the operative field is prepared. The anticipation of the operation and excitement usually attendant upon the induction of anesthesia, sometimes producing fatal shock, are by this method eliminated. "Up to this point the patient's brain, hence the remainder of the body, is in a negative state, and this is half of the innovation of the specialized operation; the other half is this: any injury of any sensitive part of the body, though the patient is under inhalation anesthesia, ex- cites the brain, and hence, through the brain, all of the motor mechan- ism, especially the thyroid. Inhalation anesthesia is but a thin veneer, and, although the patient is unconscious, the afferent impulses set up by the operation reach the brain apparently as readily as if no anesthetic was given. "This is the source of the hyperthyroidism, so called, that constitutes the greatest danger of the operation. Operation under inhalation anes- thesia on any sensitive part of the body produces precisely the same ex- acerbation of the disease (hyperthyroidism) as operations upon the thy- roid gland itself. How may this be avoided ? It may be wholly avoided by the use of complete local anesthesia in addition to general anesthesia, by the use of novocain throughout the entire operation, just as com- pletely as if the patient had received no general anesthesia." "By this technique," Crile states, "the scope of the operation is greatly increased and the gland can be safely removed from any patient whose condition will endure the metabolic influence of the sudden with- drawal of so much active gland tissue." With operations upon the hrain, it is better to use chloroform and oxygen. Nitrous oxid and oxygen are contraindicated, as they raise ar- terial tension with unnecessary bleeding. For the same reason ether should be avoided as a preliminary, as any struggling will immediately induce congestion with increased bleeding. In an emergency case, or if the patient is unconscious, preliminary medication should be avoided. Amputations. — For amputations, dislocations, setting fractures, and similar operations, preliminary medication is essential, and a fairly deep anesthesia should be used. Gas and oxygen by some closed method is preferable for work of this character. Operations Upon Fingers and Toes. — Operations upon fingers and toes require a deep anesthesia in order to avoid reflex movements, on account of the unusually large nerve supply in these parts. ANESTHETIC AND TECHNIQUE FOR SPECIAL OPERATIONS 355 Circumcision. — For circumcision of a child the hcst plan is to start with one or two drops of the essence of bitter orange peel and supplement this with chloroform drop by drop until the second stage is reached, when a switch to ether by the drop method is instituted. A change to the closed method may then be advantageously made. The anesthesia should be considerably lessened before the final dressings are applied. Rectal Cases. — All rectal cases should have full physiological doses of morphin with some other drug. The anesthesia can be induced and maintained with nitrous oxid and oxygen or ether by the closed method. Chloroform should be avoided in these cases. Obstetric Cases. — In obstetrical practice, on account of the enlarge- ment of the heart at that period, and the patient always welcoming the anesthetic, chloroform with oxygen is preferred, and is unattended with the immediate risk that might be inseparable from chloroform at an- other time. An additional reason for chloroform being safe at this time is the continuous dilatation of the sphincters of the uterus and vagina, compelling the patient to take deep breaths, and thereby get rid of the anesthetic almost as soon as administered. A deep anesthesia is not indicated at any time, both on account of the child and the mother. The anesthesia should be maintained between the second and third stages if possible. The reported fatalities from chloroform in this connection are exceedingly rare, and are usually due to gross carelessness, ignorance, or attempting to maintain too deep an anesthesia. If ether is used it can easily be deodorized by the vapor method. Kitrous oxid and oxygen given to the stage of analgesia is becoming more and more popular. Anesthesia should be avoided during the menstrual period, as there is a greater possibility of hysterical or maniacal excitement afterward. If, however, an operation is imperative, a warm oxygenated chloroform vapor is indicated. Curettage. — For curettage or similar operations, nitrous oxid and oxygen, or warm chloroform vapor with oxygen or air, if the type of patient permits, is best. Genito-urinary Operations. — In genito-urinary operations, where deep anesthesia is always required, the nitrous oxid-ether sequence is in- dicated. Laparotomy. — In laparotomies, where absolute relaxation is required, the nitrous oxid-ether sequence, to- be followed by chloroform when the patient is in the Trendelenburg position, is the combination preferred by such men as Hewitt ^ and Boyle. ^ Boyle's routine procedure is to change to chloroform or the chloroform-ether mixture after fifteen or twenty minutes. Chloroform is administered with less danger when the patient is in * Hewitt : ' ' Ansesthetics. ' ' ^ Boyle : ' ' Practical Anaesthetics, ' ' 142. 356 ANESTHESIA the Trendelenburg position, on account of the large amount of blood in the brain at that timfe. Eelaxation of the abdominal musch^s is assisted by placing a sandbag under the knees and slightly raising tlie shoulders. Gastro-enterostomy and Similar Operations. — In addition to the usual preliminary preparation, Crile's method is as follows : "Starved and Anemic Patients. — A preliminary transfusion of blood brings back the vitality of patients exsanguinated by hemorrhages and makes them good risks; thus the surgeon may reclaim the bad risks in hemorrhage from ulcer of the stomach or duodenum. "In starvation cases the risk cannot be so successfully reclaimed, though the patient may be much improved by transfusion. The risk in these cases is not shock and depression, but a broken metabolism ex- pressing itself as acidosis. "Since employing transfusion I have had the opportunity of seeing more clearly the dangers of acidosis, for I have operated on cases all but moribund, and have seen them pass through the operation unchanged, and have seen metabolic death follow. Heretofore such cases would not have been operated, and if operated would not have survived long enough for study. There is a stage of acidosis rather easily recognizable which proves fatal as a metabolic process in spite of complete control of the blood volume, and measurably of the blood pressure. This does not in the least apply to acute or chronic hemorrhage. Here transfusion gives an absolute control." Crile states, further, that "the combination of nitrous oxid, general anesthesia, and novocain, local anesthesia and quinin, and urea hydro- chlorid as a post-operative anesthesia combined with ample incision and gentle handling establishes anoci-asso elation — or shockless operation." Other surgeons get excellent results by starting a hypodermoclysis as soon as the patient is in surgical anesthesia and continuing this throughout the operation. As much as two quarts of normal saline can be taken by a patient in this way with splendid results. With the vapor method of ether anesthesia, the patient's pulse can be easily maintained at normal, provided the surgeon is gentle in his manipulation. Peritonitis or Intestinal Obstruction. — If morphin has been used to quiet pain the anesthetist should be informed of this fact. Otherwise too deep an anesthesia may be instituted at the commencement of the operation. Surgeons here should not insist upon absolute relaxation, as in many cases it is almost impossible to maintain this condition. If regurgitation of fecal matter is present, the stomach should be well washed out before the induction of the anesthetic and the stomach tube left in place during the operation. The open method of administration should be used, initiated preferably with chloroform and continued with ether. If vomiting occurs, the anesthetist must immediately insert a mouth gag (but must not pull the tongue forward) and with his finger ANESTHETIC AND TECHNIQUE FOR SPECIAL OPERATIONS 357 or a sponge on a sponge holder keep the throat absolutely clear. Death by suifocation is always imminent in these cases. CONCLUSIONS With these general indications as a guide, it can readily be seen how- impossible it is to say that some one anesthetic should be used at a cer- tain age, or for a given disease, or for some specific operation. The con- ditions blend in such a way that the anesthetic must be selected for each case; the safety of the patient, and the successful termination of the operation, being the results sought. If the surgeon is so situated that he must work without a trained assistant and without the refinements of anesthesia customary in the larger cities, ether should be the anesthetic of choice. Finally, when thus handicapped, the surgeon should always remember that it is possible with morphin and whiskey, plus a very small amount of general anesthetic, to complete successfully nearly any operation. Fatalities have unquestionably occurred from the use of some one anesthetic or method. No hospital or clinic can be considered to rank among the first when a routine procedure is countenanced. When for any reason, after careful choice and deliberation, the anesthetic is taken badly a change should be made immediately, BIBLIOGRAPHY Abelin : Jalirl. f. Kinderhr., 1870, 55, 116. Adami & Nicholls : "Principles of Pathology," 2, 697. Albwot : "System of Medicine." Bagensky : Cejit. Zeit. f. Kinderh. Bartel, J. : "Ueber die hypoplastische Konstitution und ihre Bedeu- tung," Wien. Jclin. Wclmsclir,, 1908, 21, 783-790. Barten & Stein: "Ueber abnormale Lymphdrusenbefunde und deren Beziehung zum Status thymicolymphaticus," Arch. f. Anat. u. Entwichlungsgescli., Leipz., 1906, 231-249, 3 pi. Von Bardeleben : Arch. f. hlin. Chir., ^6, 149. Beneke: Berl. hlin. Woch., 1894, 31, 216. Biechele, E. A. : "Status Lymphaticus with a Eeport of Cases," Arch. Pediat., New York, 1904, 21, 500-508. Biedert: lUdem, 1896, 33, 581. Blake: Ann. of Surg., 1902, 35. Blumer: Johns Hopkins Hosp. Bull., Oct., 1903, 11).. Bonnet: Gaz. des Hopitaux, Dec. 9, 1899. Bovaird, D., Jr. : Arch, of Pediat, 1906, 23. Bradley, E. B. : "Death Under Anesthesia Due to Status Lymphaticus," Jour. Am. Med. Assn., Chicago, 1910, 59, 1785. 358 ANESTHESIA Brickner: Foster's "Therapeutics, Ether.". Carlyll, H. B. : "The Thymus Gland and the Status Lymphatieus/' Guy's Hosp. Rep., Lond., 1910, 6Jf, 1-37, 1 pi. Clessin: Munch, med. Woch., 55, 330-1898. Cocks, G. H;: "Status Thymo-Lymphaticus and Its Eelation to Sud- den Death," Ma7i. Eye, Ear & Throat Hosp. Rep., N. Y., 1911, 12, 199-216. Conner, L. E. : "The Clinical Diagnosis of Status Lymphatieus," N. Y. Med. J., New York, 1906, 6, 283-284. Coolidge, E. L. : "Status Lymphatieus, Eeport of a Case." Bull. Ly- ing-in Hosp., K. Y., 1908, J^, 149-151. Daut : Jahrb. f. Kinderhr., 1898, ^7, 14. Day : "Another Case of Status Lymphatieus," Pediat., IST. Y., 1910, 22, 428-433. Ehrhardt : Arch. f. Min. Chir., 78, 598. Epstein : Milnch. med. Woch., 1902, ^9, 1728. Escherich: Berl. Min. Woch., 1896. 33, 645. Ewing: "The Lymphatic Constitution." iV. T. Med J., July 10, 1897, 37. Farret : These de Paris, 1896. Quoted by Hotz. Fer: Corr. f. schwei. Aertze, 1904, 3J^, 2. Fischl : MUnch. med. Woch., 1902, Jf9, 1728. Flugge: Vrtljschr. f. gerichtl. Med., 1899, 17, 20. Friedjung: Centralhl. f. d. Grenzgeh. d. Med. u. Chir., 1900, 111, 465. Friedlander: Arch, of Ped., 1907, 2J^, 490. Friedleben : Die Physiologic der Thymusdrilse, 1858. Ganghofer: Milnch. med. Woch., 1902, Jf9, 1728. Gardner: "Lymphatism," Proc. Roy. Soc. Med., Lond., 1909-10, 111, Sect. Anesthesia., 19-44. Gluck: Berl. hlin. Woch., 1894, 31, 670. Grawitz : Deut. med. Woch., 1888, 12, 429. Griffith: Trans. Ass. Am. Phys., 1903, 18. Halsted: Phila. Med. J., 1900, 859. Harris: "The Laryngoscope," Feb., 1910, 199. Hart : Centralhl. f. d. Grenzgeh. d. Med. u. Chir., May to August, 1909. Hedinger: "Ueber die Kombination von Morbus Addisonii mit Status Lymphatieus." Franhf. Z. f. Path., Wiesb., 1907, 1, 527-543, 1 pi. "Ueber Beziehung zwischen Status Lymphatieus und Morbus Ad- disonii." Verhandl. d. deut. path. Gesell., 1907; Jena, 1908, 11, 29-32. Henderson, Yandell : "Primary Heart Failure in Normal Subjects Un- der Ether," Surg. Gynec. & Ohstet., Aug., 1911, 161-165. Heussler: Deut. med. Woch., 1894, 38. Hinrichs : Berl. hlin. Woch., 1908, 1^5, 825. ANESTHETIC AND TECHNIQUE FOR SPECIAL OPERATIONS 359 Hotz : Beit. z. Min. Chir., 1907, 55, 525. Howland: "The Symptoms of Status Lymphaticus in Infants and Young Children." Tr. Am. Pediat. Soc, Phila., 1907-08, 19, 51-59; also, Proc. Path. Soc, Phila., 1909, 12, 267-276. Humphry: "Clinical and Post-mortem Observations on the Status Lymphaticus with Deductions and a Plea Against the Maligning of Ethyl Chlorid as a General Anesthetic.'* Lancet, Lond., 1908, 11, 1870-1874; also, J. Ment. Sc, Lond., 1909, 55, 473-481; "Status Lymphaticus," Lancet, Lond., 1909, 11, 1703-1705. Jackson: J. Am. Med. Assn., May 25, 1907. Jessen : Aerz. sachver stand. Zeit., 1898. Kassowitz : Miincli. med. Woch., 1902, 49, 1728. Kauffmann: "On Two Cases Suggesting Eelationship to Status Lym- phaticus." Rep. Soc. Study Dis. Child., Lond., 1907-08, 8, 435-438; also, Birmingh. Med. Rev., 1908, 6Jf, 182-184; also, Brit. J. Child. Dis., Lond., 1908, 5, 430-432. Kern: "Status Lymphaticus." J. Indiana Med. Assn., Fort Wayne, 1909, 2, 480-482. Koch: "Status Lymphaticus mit Persistierendem Thymus." Deut. med. Woch., Leipz. u. Berl., 1911, 37, 1102. "Mechanische Thy- mus — Erstickungstod mit Status Lymphaticus." Konig: Central, f. Chir., 1897, 2Jf, 605. Verhandl. d. deut. Gesell. f. Chir., 1898, 35, 119. Kopp: DenTcwiirdigJceiten, 1830, 1. Krause & Cohen: Deutsche med. Woch., 1890, 450. Kundrat : Wien. hlin. Woch., Jan. 3, 10, 17 and 24, 1895. Lange: Jahrh. f. KinderTcr., 1898, 48, 119. Marfan : Bull. Soc. Hopit., 1894, 11, 361. Mau: "Enlarged Thymus and Sudden Death." Med. Chron., Man- chester, 1910-11, 53, 216-223. 1 pi. McCardie: "Status Lymphaticus in Eelation to General Anesthesia." Brit. Med. J., Lond., 1908, 202, 196. Munro : "The Status Lymphaticus." Lancet, Lond., 1909, 2, 1468. Musser & Ullom: "A Case of Status Lymphaticus." Med., Detroit, 1904, 10, 351-359. Also reprint. Nettel : "Ueber einen Fall von Thymustod." Arch. f. Iclin. Chir., 1904, 73, 636. Nordmann: Correspond, f. schweiz. Aerzte, 1889, 202. Norton: Phila. Med. J., 1898, 249. Gehme: "Lymphfollikel im kindlichen Knochenmarke." Miinch. med. Woch., 1909, 56, 446-449. Ohlmacher : J. Am. Med. Assn., Feb. 13, 1904. Paltauf : Wiener Min. Woch., 1889. Park: "The Status Lymphaticus." Tr. Am. Surg. Assn., Phila, 1905, 360 ANESTHESIA £3, 241-250. Also, Surg. Gynec. & Ohstet., Chicago, 1905, 1, 140- 145. Also, St. Louis Med. Rev., 1906, 53, 394. Penkert: Deut med. Woch., 1902, 28, 810. Plater : . "Observatorium in Hominis Affectibus Plurisque, etc." libri tres, 1614, 111, 172. Purrocker: Munch, med. Woch., 1899, Jk6, 943. Eachford: Tr. Assn., Am. Phys., Phila., 1910, 25, 570-579 ; also. Am. J. Med. Sci., Phila. and N. Y., 1910, UO, 550-557. •Eanke : Ibidem, 1902, 49, 1728. Eehn : Verhand. d. deut. Gesell. f. Chir., 1906, 35, 2, 364. Eichter: Miinch. med. Woch., 1902, 49, 1728. Eoberts : "The Status Lymphaticus with Particular Eeference to Anaes- thesia in Tonsil and Adenoid Operations," Tr. Am. Laryngol. Bhinol. and Otol. Soc, St. Louis, 1908, 507-524. Eubra & Brown: "Note on a Case of Status Lymphaticus with Eefer- ence to the Administration of Anaesthetics." Lancet, Lond., 1907, 11, 1759. Satterlee: "A Case of Status Lymphaticus." Arch, pediat., N. Y., 1909, 25, 689-692. Discussion, 702. "Status Lymphaticus." Brit. Med. J., Lond., 1909, 1, 1042. Schultz : Beit. z. klin. Chir., 1901, 638. Schwinn: J. Am. Med. Assn., 1908, 2059. Siegel: Berl. klin. Woch., 1896, 33, 887. Simon & d'CElsnitz: Bull. Soc. Pediat, 1902, 26. Soderland & Backman : "Studien of ver Thymusinvolutionen." Upsala Lokarefor Forh., 1908, 13. Sorgo : Central, f. Grenzgeh. Med. u. Chir., 1898, 6-10. Starr: N. Y. Med. News, 1896, 421. Targhetta: These de Paris, Jan., 1902. Thremich: Vrtljschr. f. gerichtl. Med., 1901, 21, 300. Todd & Emery: "Specimens from a Case of Status Lymphaticus." Rep. Soc. Study Dis. Child., Lond., 1903, 1904, 4, 293-296. Vintras: "Status Lymphaticus." Lancet, Lond., 1907, 1, 295. Yon Werdt. "Zur Frage der Beziehung swischen Status Lymphaticus bzw. Thymolymphaticus und Morbus Addisonii." Berl. klin. Woch., 1910, Jf7, 2383-2386. Warthin: "The Pathology of the Status Lymphaticus with Lantern Demonstration." Am. J. Ohst., K. Y., 1909, 60, 348-356. Weigert: Berl. klin. Woch., 1906, 887. Wheelock: "Anesthesia in Lymphaticus." Toledo M. and S. Rep., 1909, 35, 395-399. Wiesner: "Gefiissanomalien bei sog. Status Thymicolymphaticus." Verhandl. d. deutsch. path. Gesellsch. Jena, 1909, 217-219. Witmer : Beitr. z. klin, Chir., 29, 189. CHAPTER IX TEEATMENT BEFOEE, DURING, AND AFTER ANESTHESIA Duties of the Anesthetist in Addition to Giving Anesthetic. The Anesthetist's Kit: Anesthetist's Motto; Mouth Gag; Con- tents of Kit ; Emergency Treatment to Insure Breathing. The Management of Ordinary Cases : Preliminary Treatment ; Treatment During Anesthesia; After-Treatment. Management of Difficult or Unusual Cases: Respiratory; Muscular; Nervous; Idiosyncratic; Shock; Post-Anesthetic Toxemia. DUTIES OF THE ANESTHETIST IN ADDITION TO GIVING THE ANESTHETIC The anesthetist who thinks his duties comprise getting the patient under, maintaining narcosis until the surgeon gives the signal to Jet up, Fig. 135. — Supporting Jaw to Maintain Free Airway with Two Fingers on the Carotid Artery. and seeing to it that the patient is safely removed from the operating table to the bed is doomed to failure. Much more than this devolves upon him. He must be assured that the proper preliminary hygienic, 361 362 ANESTHESIA psychic, and medicinal preparation is attended to; he must find out whether the breathing is oral or nasal, and direct his anesthetic vapor ac- cordingly; he must keep a clear airway either by manipulating the lower jaw or by a suction pump or sponging; he must maintain an even nar- cosis; he must keep the mouth gag (if used) in position; he must pro- tect the patient from too much pressure upon the throat and chest either from artery forceps, or from an assistant or anyone leaning too heavily upon the chest; he must assist the surgeon in any way that may be de- sirable, according to the exigencies of the case. He must be equipped for the management of all manner of emergencies which may concern his part of the surgical procedure or the after-treatment of the case. In order to meet the exigencies, whatever their nature, as they arise, the following equipment will be found invaluable: THE ANESTHETIST'S KIT Anesthetist's Motto. — The difficulty with all inhalation methods of administration, as before mentioned, is respiratory. While the motto of the anesthetist should be Anticipation, yet there sometimes occur cases in which asphyxial symptoms take such a course that interference is necessary in order to retain a clear air passage. Mouth Gag. — The skilled anesthetist seldom uses a mouth gag and tongue forceps. In thousands of cases it should not be necessary. (This does not apply to cases in which the mouth is to be operated upon.) Nevertheless, the anesthetist should always be prepared to use both. Contents of Kit. — The following is a list of the apparatus that should be convenient wh^enever an anesthetic is given, regardless of the method : (1) A wooddii gag or screw with which to open the mouth. (2) Mouth gag, so patterned that the blades will fall one behind the other when closed, this being the easiest to place between the teeth. (3) Tongue forceps. The best tongue forceps have a small projec- tion to clasp the tongue directly in the middle. If this is placed in the median line, there will be little or no bleeding, as there are very few blood vessels and nerves in this part of the tongue. The tongue is really composed of two parts joined in the median line. The tongue forceps with two projections will invariably cause a flow of blood. (4) A tracheotomy set. This should be in a case, every part steri- lized, and ready for use. It should not be open unless an emergency calls for its use. (5) A curved needle threaded with silk, sterilized, and wrapped up. (6) A hypodermic syringe. Emergency Treatment to Insure Breathing. — Whenever the anesthet- ist anticipates trouble of any kind, he should examine the mouth of the TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 3G3 patient, and, if tliis is not clone before the administration, it requires but a second to open the lips and determine immediately which side of the mouth will be the best in which to place the wooden wedge or screw. Before placing the wedge or gag in the mouth, however, the anesthetist should exhaust every plan to have the patient breathe natu- rally. If unsuccessful in this, while every second counts in an emer- gency, it is unnecessary to destroy or injure the patient's teeth. After the mouth has been opened sufficiently with the wooden screw, place the mouth gag in position, insert the tongue forceps in the median line, one-half to one inch from the tip of the tongue, and pull the tongue forward. If an airway is thus secured, and the patient recommences breathing, it is always best to then remove the tongue forceps and gag. Nevertheless it must be borne in mind that, if such a procedure has be- come necessary once, it is likely to recur at any time. Very little trac- tion is necessary to pull the tongue forward. In addition to moving the jaw and head in different directions, one of the best means of overcom- ing asphyxial symptoms is by placing a tube from the oxygen tank in the nose or the mouth. If a stream of oxygen has to be kept up in this way during the remainder of the operation, the patient will be no worse for it. Again, the anesthetist must bear in mind that, if in the midst of an operation asphyxial symptoms continue to assert themselves, it is always possible to considerably diminish the amount of pulmonary anesthetic by administering a hypodermic of morphin. For excision of the tongue, or any operation in which it is necessary to hold it forward for any length of time, a thread would be less in the way than the tongue forceps. The needle should be inserted in about the same place as the tongue forceps, the thread pulled through and tied in a convenient loop, and the needle cut off. The thread may then be caught with an artery forceps. It is the purpose of this chapter to give, in condensed form, certain practical suggestions concerning the management of surgical cases, from the anesthetist's point of view. It is now well known that the success of the anesthesia as regards the ultimate Recovery of the patient is largely dependent upon the preliminary preparation, the treatment during the course of the narcosis, and the care after the anesthesia is discontinued. In order to render this part of the present volume as available as pos- sible for practical purposes, the subject is divided into: (1) The man- agement of ordinary cases before, during, and after anesthesia; (2) the management of difficult and exceptional cases before, during, and after anesthesia. 364 ANESTHESIA THE MANAGEMENT OF ORDINARY CASES Under this category come the ordinary run of surgical cases — pa- tients who need, perhaps, a certain amount of suggestive therapy along with the requisite medicinal treatment, regardless of the anesthetic agent to be employed. Preliminary Treatment The preliminary preparation of a patient about to be anesthetized may be : ( 1 ) Hygienic ; ( 2 ) psychic ; ( 3 ) medical. Some patients re- quire one or the other; others require all the preliminary adjuvants that may be brought into requisition. Hygienic. — Grooming of Patient. — The patient should be as thor- oughly prepared (as far as his or her condition permits) as if for an ath- letic event. A warm bath with thorough cleansing of the skin and a shampoo for the hair, followed by an alcohol rub, should precede all other treatment. Eemoval of hair over and adjoining site of operation with scissors and razor should be done the night previous to a morning operation, or in the morning for an afternoon operation. "One of the most essential points in preparing the patient for operation is to make sure that the preceding night is a restful one. If the patient is in pain, or is particularly nervous, a hypnotic should always be admin- istered." ^ The Mouth and Kose. — If possible, a dentist should cleanse the teeth thoroughly, removing loose and hopelessly decayed teeth, and then giving the patient a suitable antiseptic mouth wash to be used every four or five hours until time for the operation. This wash should be used to cleanse the nasal passages as well. "The disinfection of the mouth is a matter of so much importance in the prevention of pneumonia from aspiration during anesthesia that it should never be neglected.^' Hydrogen dioxid, one part to three of water, or potassium permanganate in a weak solution, may be used for this purpose. The Bladder. — "Patients should eithjer empty the bladder or be catheterized immediately before the operation. "If urine is scanty, bicarbonate of potash or citrate of potash in small quantities, not more than 30 or 30 grains within twenty- four hours, added to pure water should be given freely to flush the kidneys. "Should a more active diuretic be desired, small doses of sweet spirit of niter may be added to the draft, since this simple remedy acts as ^ ' ' American Practice of Surgery, ' ' 4, 132. TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 365 an efficient diuretic, in many cases overcoming any tendency to spasm of the renal vessels and flooding these organs witli blood. "^ Intestinal Tract. — No athlete is ever given a purge on the night immediately preceding a contest, and the time should be past when a patient is thus debilitated before entering the operating room. All are agreed on the advisability of emptying the intestinal tract, the method and time of doing this varying with different hospitals and surgeons. "Two days before the operation the patient is given one or two table- spoonfuls of castor oil or a dessertspoonful of natural Carlsbad salts in a glass of warm water, or at noon on the day before the operation a purgative should be given, followed in eight or nine hours by an enema, the amount of purging being increased or diminished according to the patient's strength. "In intestinal obstruction, with frequent vomiting or regurgitation, a careful insertion of the stomach tube, which may be left in place, is necessary before commencing the anesthesia. "The bowels should not act more than twice in the twenty-four hours previous to the operation. Many surgeons dispense entirely with purga- tion, as the worst condition of all is when the patient is suffering from an artificial diarrhea at the time of operation. The number of bacteria increases as the intestinal contents become more liquid, and diminishes with the abatement of the diarrhea. *'^The intestinal tract should be cleansed and practically emptied be- fore the time of operation. Two ounces of castor oil are administered 12 to 16 hours before operation, ■ and the large bowel is emptied by a soapsuds enema on the morning of the operation. The cleansing of the entire intestinal tract, together with the withholding of nourishment, renders the canal practically sterile in its upper portions, facilitates intra-abdominal manipulation, and lessens the possibility of gaseous dis- tention after the operation. The administration of sterilized foods is also a good procedure." ^ Diet. — "While advantageous to have the stomach empty, it is not essential to starve the patient for twelve or eighteen hours. Easily di- gested gruels of barley or rice can be given in small quantities up to within two or three hours of the operation with distinct advantage. Starchy gruels permit the liver to store up glycogen and thereby place it in a favorable position for maintaining its function. Animal broths throw an undue strain upon the kidneys in the elimination of extrac- tives. Hunter believes that the absence of glycogen from the liver, by diminishing the combustion processes in that organ, diminishes the anti- toxic power of the liver cells, so that the starved individual is more 'Keen's "Surgery," 5, 1008. ^Am. J. Surg., 4, 131. 366 ANESTHESIA easily affected by poisons than the glycogen-rich person. So, too, an absence of carbohydrate material results in extensive changes in fat metabolism, which results in an increased formation of acid, and so tends to the development of acidosis." ^ "The patient should be kept in bed and given liquid diet for eighteen hours prior to the operation. Water is freely given by mouth up to within three hours of the time of operation. The practice of withhold- ing water involves unnecessary hardship and discomfort, while its free administration aids materially in the subsequent elimination of ether, and is undoubtedly a factor in preventing the possibility of shock. When inadvisable to give water by mouth, one-half pint of normal saline may be administered per rectum two hours before the patient goes on the table." 2 Psychic. — Some patients, as we have stated, require one or all forms of preliminary preparation in order to insure a smooth, safe, and alto- gether satisfactory anesthesia. The expert anesthetist must be able to judge of the particular requirements of the individual case. Over seventy per cent of cases, according to conservative estimates, require both mental and medical treatment in order to insure the best results. Children and nervous and irritable adults require psychic preparation for the coming ordeal, and the anesthetist who ignores this factor runs the risk of having to deal with more or less serious difficulties during some portion of the time when the patient is under his care. In this con- nection the Chapter on Hypnotism will be found helpful. Idiots and insane persons, as a rule, require only medical prepara- tion. In many cases, however, in which the mental defect is of a mild degree of severity, the patient is susceptible to the reassuring influence of a calm and forceful personality. Those who have had occasion to wit- ness operations in homes or hospitals for defectives or the insane have observed this. The senior author (J. T. G.) recalls the case of a feeble- minded boy who, when about to be operated upon for the removal of adenoids and tonsils, flew into an uncontrollable rage at the sight of one anesthetist, who made no pretense of giving the patient the benefit of suggestive therapy, whereas another anesthetist, availing himself of this aid, experienced no difficulty in getting the child to take the anesthetic quietly. Patients already in a state of coma require no preliminary treat- ment. Necessity for Preliminary Mental Preparation. — "There can be little doubt that the mental condition of the patient does not receive enough attention from the average anesthetizer. It is remarkable that patients, whose thoughts are made to run in pleasant channels as the an- » Keen 's ' ' Surgery, ' ' 5, 1000. '"American Practice of Surgery," 4, 131. TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 367 esthetic is first given, usually take the drug more quietly than those who inhale it in a condition of mental distress. This is particularly true of nervous women and children. When the fears of a patient who is con- scious are developed into the terrors of semiconsciousness, in which the patient imagines the most frightful accidents are taking place, it can be readily understood that profound nervous shock is produced." ^ "Where but little is required to turn the scales toward the side of death, unquestionably fear may sometimes lead to fatal results through psychical shock, through the lack of cooperation of the patient in declin- ing proper nourishment, through loss of sleep, and finally through im- paired resistance, which results from the combination of these factors. Such extreme dread as is referred to here should be carefully considered, so that every effort may be made to soothe the fears of the sufferer, as the successful outcome of an operation sometimes materially depends on the tranquilized state of the patient's mind. It is often not the most formidable and dangerous operations which thus terrify patients, and it is not always the hysterical or simple-minded who are the victims of this dread. Psychical shock, although rarely fatal of itself, may readily prove a determining lethal factor in a patient with unsound organs, who is ttlso subjected to the physical shock and loss of blood of an operation." ^ Crile states that : "Although there is not convincing proof, still there is strong evidence that the effect of the stimulus of fear upon the body withoat physical activity is more injurious than the effect of fear with physical activity. It is well known that the soldier lying under fire waiting in vain for orders to charge suffers more than the soldier that flings himself into the fray ; that a wild animal in an open chase against capture suffers less than when cowering in captivity." If this is true, exactly the same state exists when a patient lies in bed awaiting an operation. Crile goes even further, and states : "That the brain is definitely influenced, even damaged, by fear has been proved by the following experiments: "Eabbits were frightened but not injured, and not chased, by a dog. After various periods of time the animals were killed and their brain cells compared with the normal. Widespread changes were seen. The principal gross phenomena expressed by the rabbit were rapid heart, accelerated respiration, prostration, tremors, and a rise in temperature. "The dog showed similar phenomena, excepting, instead of muscular relaxation, as in the rabbit, it showed aggressive muscular action. Both the dog and the rabbit were exhausted and, although the dog exerted himself actively and the rabbit remained physically passive, the rahbit was much more exhausted than the dog. "Other observations were made upon the brains of foxes chased for * Keen's "Surgery," 5, p. 12. 'Am. J. Surg., 4, 120. 368 ANESTHESIA various distances by members of a hunt club, then finally overtaken by the hounds and killed. The brain cells of these foxes as compared with those of a normal fox showed extensive physical changes/' Illustrations Showing Necessity for Mental Treatment. — There is recorded the history of a patient in whom the psychic element predominated to such an extent that the patient suddenly expired dur- ing the shaving of the groin, preparatory to an operation for hernia.^ There is a record of another patient whose dread of the anesthetic was such that the narcotiser dropped water upon the mask for a few min- utes with the idea of assuaging his anxiety and distress of mind, but even this procedure did not prevail, and the patient died before a single drop of chloroform touched the mask.^ A patient at Bellevue Hospital, in N"ew York City, cut his throat in anticipation of an operation which was to be performed upon him the following day. A patient (in private practice), who had been given only a few breaths of nitrous oxid, jumped from the table, fled from the room, and was never afterward located, so far as operation was concerned, by the surgeon.^ We see the other extreme in obstetric practice. The patient always welcomes the chloroform, as she is in such a state of mind that she is willing to do anything to relieve her suffering. The vast majority of surgical cases come between these two extremes. Mental Depression. — It is interesting to note that the majority of fatal cases reported, in which the psychic element predominated to such an extent that a fatality resulted, were men, and these are the patients who have this mental depression. Not only so, but they are men in ro- bust health, requiring possibly but a slight operation. In the light of these statistics, it is wrong to place an alcoholic or an athlete upon the table without endeavoring to eliminate this psychic element. Diagnostic Evidences of Fear. — In spite of the fact that most patients claim not to be fearful of the ordeal through which they are to pass, and possibly present no outward manifestation of fear, the anes- thetist, listening to the heart of the patient just before the administra- tion, discovers that things are not what they appear to be on the surface. In a great many instances the palpitation of the heart is alarming, and seems to be absolutely out of the control of the patient. In a great many others the heart is beating faster and with more force than normal. This state of affairs means that, when the anesthetic is finally adminis- tered, the patient is in an attitude to resist the effects of the anesthetic. ^Sir James Y. Simpson's work, 2, 144. ^Kappeler: " Anajsthetics, " 118. ^ This case was reported to the senior author by the surgeon. TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 369 On the other hand, even though the patient may say that she is afraid (men never admit it), if this patient has had the proper preliminary medication, the heart will be found normal. In other words, the nerv- ous mechanism has been taken out of the patient's control temporarily; not only so, but the mind is now in a condition where a few suggestions in the proper spirit and manner are readily grasped by the patient. When the patient, thus doubly prepared, has the anesthetic administered, the chances are all in favor of a sleep approaching that of nature. "The transition from partial sleep to complete anesthesia is not so sudden as from complete wakefulness, and is more easily accomplished." (Crile.) Influence of Omission of All Preliminary Medication in Pos- sible Subsequent Operations. — When this preliminary medication is omitted, even if everything goes on, to all appearances, smoothly, the patient's condition of mind as he approaches the operating table may come back to him at some future time when a second operation is needed, and so act upon his nerves as to make him defer the operation until, possibly, too late for anything but palliative surgery. Importance of Preliminary Medication. — Not only is a patient in a proper frame of mind to receive suggestions when preliminary medi- cation is used, but the whole nervous system is obtunded, especially the olfactory nerve and the vomiting center. The patient, therefore, takes more kindly to the anesthetic, passing quietly and quickly into full sur- gical anesthesia. If, during the operation, it is possible to lighten the anesthesia without disturbing the surgeon, the patient can be held be- tween a light and deep narcosis without once disturbing the dangerous vomiting center. The patient comes out, as a usual thing, without either conscious or unconscious vomiting. The kidneys and lungs have also been saved unnecessary irritation by thus reducing the amount of pul- monary anesthetic one-third to one-half. Even when this element of fear is seemingly entirely absent, the pa- tient, disregarding preliminary treatment of all kinds, incurs a certain definite and needless risk, often out of all proportion to the operation to be performed. A gentle laxative, rest in bed at the place of opera- tion, and a small physiological dose of morphin or some other sedative should be insisted upon for even slight operations. Two illustrative cases from the writer's and one from a noted sur- geon's practice in ISTew York City will suffice. (1) Adenoid and tonsil case of a young girl twenty-two years of age. She refused to stay in a private sanitarium over night, and conse- quently did not have any morphin preliminarily. Patient walked in from the street, and, while the surgeon and myself retired to another room, disrobed and laid herself upon the table, and was draped by the nurse for operation. Heart sounds normal and no outward, appearance of nervousness. Induction of anesthesia uneventful. About two min- 370 ANESTHESIA utes after beginning the operation patient stopped breathing, and after the usual procedure was revived and the operation completed. Patient was compelled to stay in hospital for two days on account of laxity of the sphincter ani, and the surgeon was put to his wits'" end to explain the relation of this condition and subsequent diarrhea to the adenoid and tonsil operation. (3) Patient, male, sixty-five years of age. Carcinomatous gland of neck. Patient walked into hospital on the morning of the operation, and had no preliminary medication before coming to the operating room. Heart slightly hypertrophied and sometimes failed to compensate. After operation had progressed about fifteen minutes, respiration ceased for no apparent reason except lack of preliminary treatment of all kinds. A quick slap on chest wall over precordial region failed to start the respira- tory pump. The head of the table was quickly lowered; sphincter ani stretched, traction on tongue and artificial respiration with massage of precordial region were immediately instituted. All of these factors acting together resulted finally in the patient's respiratory center reasserting itself, and the operation was successfully completed. (3) Patient, male, age thirty-five; vigorous health, slight operation under cocain. No preliminary medication of any kind was attempted beyond cleansing the immediate field of operation. A few drops of co- cain were injected into the urethra, when the patient immediately stopped breathing, and all efforts at resuscitation failed. The above fatal case and the two nearly fatal cases illustrate most forcibly the imperative necessity of safeguarding patients by preliminary medication in so-called minor operations. In order to completely eliminate the element of fear, Crile has elabo- rated a method which he calls anoci-association. This consists of block- ing off the nerve supply to the field of operation (in external operations) by the local or intraneural infiltration of novocain. The brain is thus completely isolated from operative influence, and, according to Crile, "is not more affected than if the operation were performed on clothing." This is of importance aside from the comfort of the patient, because, as Crile has shown, the element of fear has a definite effect on the cells of the brain. These changes, to whatever due, are always proportional to the extent of the loss of vital force. Medical.— The medical treatment consists of: (1) The treatment necessary to prepare the patient for the opera- tion, which is in part included under hygienic treatment. (2) The narcotics and hypnotics preliminarily given as a desirable part of the anesthetic. There is a complete unanimity among surgeons as to the preliminary use of morphin in local, spinal, intravenous, and rectal anesthesia. (See remarks in each of these chapters.) On the other hand, there is a wide TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 371 diversity of opinion as to prescribing morphin and other narcotics before pulmonary anesthetics, most surgeons believing thoroughly in their use, while others never employ them before an operation, but inconsistently prescribe some of them immediately afterward. As all pulmonary anes- thetics are improved by use of these drugs more than are the four spe- cial classes of anesthesia mentioned above, there should be a greater unanimity of opinion concerning their value than exists at present. EuLES Governing Preliminary Medical Preparation. — Prelimi- nary medication consists usually of morphin, hyoscin, chloretone, bro- mids, and whiskey, either alone or in combination. The following rules will assist in determining whether or not preliminary medication, and es- pecially morphin, should be used.^ (1) Whenever morphin (or other narcotic) is to be given at all, it should always be given before, instead of after, the operation, in order to obtain the benefits of it in the induction and maintenance of anesthesia. (2) After taking it, the patient must be kept in bed absolutely quiet, and at the proper time carried to the operating room. (3) All athletes, alcoholics, neurotic and plethoric patients should have preliminary medication in order to take away, as far as possible, the physical control which might enable them, when the second stage of narcosis is reached, to take a deep breath, hold it, and thus force upon the heart all the anesthetic vapor in the lungs, creating an overdose. (4) In the extremes of life, the very young, the very old, under seven and over seventy, if morphin is given at all, it should be with very great caution. (5) Whenever morphin is given a lighter narcosis should be main- tained than when this drug is not employed. (6) Care must be taken in administering the usual doses of mor- phin when chloroform is the terminal anesthetic. It is best to use some other drug, as both morphin and chloroform have a depressing effect on the respiratory centers. Atropin is the best drug to employ as a pre- liminary to chloroform (or any combintion of drugs with chloroform), rendering inhibito-respiratory reflexes less liable to occur. If used alone, atropin, 1/100 to 1/150 of a grain, 30 minutes to 1 hour before the operation, is the proper dose. One-eighth of a grain of morphin with 1/150 grain of atropin is a good combination when chloroform is used alone. Preliminary narcotic medication increases the confidence of nervous patients, lessens the amount of anesthetic required, prevents the exces- sive accumulation of mucus in the throat, reduces the liability to shock, and eases the immediate post-operative pain, while often giving to the patient a happier exit from the influence of the anesthetic." ^ 1 Collins, C. U.: J. Am. Med. Assn., Mar. 26, 1911. »^m. J. Surg., 4, 132. 372 ANESTHESIA "Through countless experiments it has been found that narcoses are possible with far smaller amounts if preceded a few hours before by a hypnotic, even though these hypnotics act on entirely different organs." ^ Time for Giving the Pkeliminaky Medication. — Whenever medi- cation is used, it should be given for its full physiological effect to be apparent Just before the time scheduled for the operation. It is just as important not to give the preliminary medication too long as too short a time before the operation. For morphin or any of its combinations, at least 30 minutes should be allowed. The physiological effect of morphin and atropin is indicated by dryness of the mouth and slight slowing of the heart and respiration. Doses of Preliminary Medicaments. — When chloretone is used alone, it is best to start at least 1 hour or an hour and a half ahead of time. Probably the best way to give this drug is 5 grains with % glass of water every 15 minutes until 15 grains have been taken. The last dose is to be given at least 30 minutes before the operation. When chloretone and morphin are used in combination, only small doses of both drugs are necessary, in order to have the desired effect. Ten grains of chloretone with i/^ glass of water, 1 hour before the time, and i/g to 1/6 grain of morphin 30 minutes before, is usually sufficient. Some experimental hiboratories report that y^ grain of morphin with 15 grains of chloretone would be absolutely safe for an athlete or an alco- holic. The average dose is 1/8 to 1/6 grain morphin with 1/150 grain atro- pin, for women; and 1/6 to 14 grain morphin with 1/100 grain atropin for men. One-eighth to 14 grain of morphin, with 1/100 grain sco- polamin 1^/2 hours before the operation has been used by some surgeons with very great success. Collins' ^ perfected technique is probably the best ever published, and for this reason is given in full. His "final choice resulted only after using hyoscin-morphin-cactin combination in 70 cases and morphin and atropin in a few cases. He first used chloroform, but in the majority of his cases ether was the anesthetic used. Lately he has been using nitrous oxid, and finds this acts equally well. This preliminary medication is given to all patients over seven years old. In exophthalmic goiter cases, on account of the nervous element, it is given the night before and repeated one and a half hours before the operation. All relatives and friends are excluded from the room, and every necessary manipulation and handling of the patient is now completed. The hypodermic is administered 1^2 hours before the operation, and consists of a solution containing scopolamin, 1/100 grain, and morphin, ^ Meyer and Gottlieb : ' ' Experimentelle Pharmakologie. ' ' ^ioc cit., 15. TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 373 1/6 grain. The room is now darkened and quiet maintained. In about 30 minutes the patient becomes drowsy and in a tranquil condition of mind. Twenty minutes before the operation a layer of gauze or cotton is placed over the eyes, and the patient is now carried and placed upon the operating table. The anesthetic is administered while the final cleansing of the opera- tive field is concluded. After the operation the patient usually sleeps from two to five hours before becoming completely awake. The smarting pain of a recent opera- tion is thus entirely eliminated. In over 1,000 cases there were no deaths and only 1 case presented unpleasant symptoms, and there was practically no post-operative vomit- ing (about 1 in 10). Indications and Contraindications or Preliminary Medica- tion. — The contraindications of morphin are the extremes of life ; acute or subacute nephritis; a state of coma; where, for any reason, the re- flexes are not to be abolished; in those extremely rare cases in which morphin is taken with distress, with accompanying disagreeable after- effects, and especially in cases of idiosyncrasy ; also very weak and feeble patients, and those with any respiratory affection. If for any reason morphin in any of its various combinations is contraindicated, an ounce of whiskey and 7 ounces of salme solution per rectum, i/o hour before the operation, usually has the desired effect of quieting the patient. When ether is contraindicated and chloroform or ethyl chlorid is the anesthetic of choice, atropin is especially indicated as the preliminary medicament to be used. It maintains the respiration, and with ethyl chlorid prevents profuse salivation with consequent nausea and vom- iting. The experimental and clinical experiences of Herrenschmidt and Beauvy ^ have made them come to the following conclusion : "That adrenal extracts should be administered to chloroformed sub- jects, whether the suprarenal capsule shows evidence of weakness or whether it gives evidence of struggle and consequent reaction. The ef- fect of prolonged chloroform administration on the medullary portion of the adrenal is diminution and even disappearance of both chromaffin and adrenalin. "Delbet has administered adrenalin to more than 1,000 chloroformed patients. The results have been splendid. He believes that adrenalin unquestionably regularizes the narcosis and diminishes (in most cases eliminates) post-operative shock." * P, Delbet, A. Herrenschmidt, and A. Beauvy : Bevue de chirurgie, Apr. 10, 1912. 374 ANESTHESIA Treatment During Anesthesia The object of treatment during anesthesia is the maintenance of the patient's vitality on as nearly normal a plane as possible. The anesthetist should at all times anticipate the needs of the sur- geon, and also give necessary directions for any treatment the patient's condition demands during the operation, for instance, during a lapa- rotomy, if a Trendelenburg posture is called for and a light anesthesia is being maintained at the time, the anesthesia should be immediately deepened, otherwise the muscles will stiffen up with the changed posi- tion and cause trouble. Again, if there is shock from handling important vessels and nerves or inflamed tissues or breaking up an adhesion, the anesthetic must be lessened and the oxygen increased, and a rectal saline or hypodermo- clysis given, thus keeping the pulse and respiration as nearly normal as possible. Hydrant Water or Saline Enema to Relieve Thirst, Prevent Nausea, and Assist Kidneys. — Furthermore, to mitigate the thirst which may arise from the morphin, to give strength and volume to the pulse and also to assist the kidneys and prevent the formation of gas in the intes- tine, two pints of normal saline solution, 105° to 115° F., per rectum materially assists in this direction, and brings the patient out in a far better condition than when this has not been included. This should be given as a routine measure, and for the special purposes here mentioned, while the patient is still in full surgical anesthesia, a slight Trendelen- burg position assisting greatly in the retention of the fluid. If the saline enema is quickly absorbed or has been given continu- ously during the operation, it may be discontinued 10 to 15 minutes be- fore the conclusion. Instead of the normal saline, ordinary hydrant water may be used with advantage, according to Trout.^ He 2 compared over 400 alternate cases. Actual experiments proved that tap water could be continued over a longer period with less rectal irritation than with any saline solution. He cites the fact that "thera- peutists sometimes obtain wonderful results in the treatment of acute and chronic nephritis by substituting a salt-free diet." He also refers to deaths that "showed experimentally that they were due to the sodium chlorid and not to the amount of water or to hemolysis." Eeference is also made to experimenters who have "actually produced not only an acute, but a chronic, nephritis in rabbits by the continual administration of this drug." He refers to Vincent, who "was able to control to a large extent a number of cases of hysteria by employing a salt-free diet with- * On the abuse of normal salt solution, see G. H. Evans: J. Am. Med. Assn., Dec. 30, 1911, 2126. 2 Trout: "Proctoclysis," J. Am. Med. Assn., May 4, 1912, 1352. TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 375 out their knowledge, and accentuated the symptoms by a corresponding increase in salt." Trout mentions specifically one of his own cases, an interval appen- dix, in which "there followed a transient alhumijiuria which remained for two days." Water was then substituted for the salt solution per rectum, and at the end of twenty-four hours the albumin had disap- peared. At the end of the next twenty-four hours, salt solution was again used and albumin appeared within the next twenty-four hours. Salt solution was then discontinued and water started, and the patient did not show any more albumin up to the time of his discharge from the hospital. In this case there was never any edema. "When a poison is introduced into the system it unites to form new compounds with the cell protoplasm, and this molecular union must be broken up before the poison can be eliminated. Salt solution has no spe- cific action in either bacterial or vegetable poisoning. "If absorption is a process of osmosis it is certainly reasonable to pre- sume that a solution which is not isotonic with blood will be more readily absorbed from the rectum, and our series of cases tends to confirm this view." "Conclusions. — (1) All patients show less rectal irritation from proctoclysis if given a soapsuds enema before the operation. "(2) The patients given water by rectum absorbed nearly 400 c. c. more to the 24 hours than did the patients given salt solution, the aver- age for the water series being 2,444 c. c. per 24 hours and the average for the salt series being 2,041 c. c. per 24 hours. "(3) The patients given salt solution by rectum required nearly twice as much water by mouth to relieve thirst, or, to give exact figures, in the water cases only 332 c. c. were taken in the first 24 hours; in the salt cases 696 were required in the first 24 hours. "(4) The amount of urine was practically the same in both cases. "(5) In 17 cases the patients complained of tasting salt without having any idea that normal salt solution was being given by rectum. None of the water series made any such complaint. "(6) In drainage cases more fluid may be taken by rectum than in those laparotomies closed without drainage. "(7) Proctoclysis should be employed more frequently than it has been in the past and in all classes of cases in which it is possible. Care should be exercised to prevent "water logging" of the entire system, and this applies to both salt and water. "(8) In peritonitis cases with drainage it is possible to have the pa- tients take four or five times as much fluid by rectum as in the cases on which this paper is based." LaAvson ^ corroborated Trout's findings. "Theoretically, at least," he 'Lawson, George B. : J. Am. Med. Assn., Apr. 18, 1908, 1267. 376 ANESTHESIA says, "it seems better in the toxemias to use plain water in place of normal saline so that the osmotic pressure would increase the absorption ; also by increasing the fluids of the body without increasing the sodium chlorid one better facilitates urinary secretion." Olive Oil to Restore the Opsonic Index. — The administration of five ounces of warm olive oil is strongly recommended by Ferguson.^ He states that "anesthesia by ether or chloroform lowers the opsonic index, that is to say, reduces the patient's power to resist an infection which was existing at the time of the operation or which may be a post-opera- tive acquirement; second, the bacteria are not materially affected either in respect to number or activity; third, this impaired resistance is brought about through the medium of both phagocytes and serum." Ferguson cites a number of experiments to prove this theory, upon both animals and human beings : "In the human experiments 5 ounces (150 c. c.) of warm olive oil were passed slowly into the rectum through a tube immediately after the patient had returned from the operating room. This was followed after three to six hours by a restoration of phagocytic power, while, on the contrary, the injection of the same amount of physiologic salt solution had no appreciable effect in shorten- ing the period of phagocytic depression." It is suggested that a certain amount of the oil is absorbed and en- ters the blood stream; and, furthermore, "in all probability a certain amount of ether is present in the intestinal tract which may be held by the oil, and thus prevented from becoming reabsorbed." Where long exposure of intestines is unavoidable, as in gastro-en- terostomy and similar operations, hypodermoclysis should be begun as soon as the patient is in surgical anesthesia, thus anticipating and in a great measure preventing surgical shock. When sudden hemorrhage occurs rectal saline, Avith the patient in a slight Trendelenburg position, will more quickly restore the volume of blood lost, and in this way reestablish circulatory equilibrium, than any other procedure. This, of course, is in addition to whatever measures the surgeon may institute for the control of hemorrhage. As a further preventive of post-operative shock, filling the abdominal cavity with oxygen at the close of the operation is a useful procedure. Aeration of Lungs. — As the operation is drawing to a close, if the anesthetic has been other than nitrous oxid, a system of aeration of the lungs should be initiated as follows : Place any mask with rubber bag over the face of a patient and com- mence pumping in warm air, the bag to be kept slightly distended or overdistended for two or three minutes and then emptied, and this * Ferguson, Eobert H. : " The Opsonic Index in Eelation to Surgical An- esthesia. " E. E. Squibb & Sons. TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 377 process is repeated (unless the patient is entirely conscious) until he is ready to be removed from the operating table. Removal of Patient. — The patient should be moved with as little jolting as possible^ and should be well covered over with hot blankets while on the stretcher, special care being taken to protect the head as well as the feet. Technique of Removal to the Bed. — Unless straps are under the Fig. 136. — Prepaking to Lift Fatiknt. Head of patient to foot of bed. patient or there is an abundance of help, instead of lifting the patient directly over the stretcher into the bed, place the head of the patient at .the foot of the bed, the stretcher and bed thus forming a right angle, with anesthetist and nurse standing within the angle thus formed. In this position a very heavy patient can be easily lifted by one, or, at most, two, people and placed in bed without Jarring or jolting and without straining the backs of those lifting. The patient should always be lifted as high as the head, in order that the principal weight of the body be carried in a vertical position. The strain upon the muscles of the back is thus materially lessened. If a sedative is indicated after the operation, it is best to use some other drug than morphin, if this has been used as a preliminary, as a repetition of morphin may induce nausea. If, however, it is repeated. 378 ANESTHESIA the atropin should be omitted, as the dryness of the throat caused by this drug is usually a source of very great discomfort to the patient. The whiskey and saline enema is one of the best medicaments to use after an ojoeration. Chloretone, in 5-grain doses, and hyoscin, either alone or combined with morphin, is also good. Einally, with proper preliminary medication, the anesthetic may be discontinued much earlier. Patients iisually continue to sleep or doze Fig. 137. — Carrying Patient Head High. This patient weighed over two hundred pounds and was easily lifted. from the morphin given for from I/2 to 1 hour after the effects of the pul- monary anesthetic have worn off. The acute pain of the operation is thus minimized and the necessity for any further medication is not so great. Aftek-tkeatment If the anesthetic has been properly administered, all reflexes should be present as the patient is being placed in bed. Two pillows should be immediately placed under the head and shoul- ders of the patient, unless indications of shock are evident. A towel should be placed over the eyes to keep out the light, and the room dark- ened but well ventilated, the patient being protected from draughts by a screen. TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 379 The saline or water enema should be repeated every few hours, unless olive oil has been given. Permit no loud talking or moving around, thus allowing the patient to sleep partly from the preliminary medication and partly from the nerve exhaustion usually accompanying any surgical operation, until he awakens from this twilight slumber in a quiet and natural manner. Water. — As soon as he is awake, free administration of either cold or hot water will make the patient comfortable. If nausea is present, and vomiting ensues, the stomach is washed out and the nausea will subside much more quickly than if the water had not been taken. This should be "further supplemented by small quantities of salt solution, 200 or 300 c. c, per rectum every 4 hours. The free administration of water not only hastens the elimination of ether, but also supplies fluid for active kidney work and militates against the occurrence of shock. After 36 to 48 hours, a liquid diet may be begun, and buttermilk, fresh milk, or lager beer, albumin water flavored with fruit juice or sherry, or tea or coffee, may be acceptable." ^ For post-anesthetic vomiting it is a routine custom among many British surgeons to give tincture of iodin, % minim (i^ minim of U. S. P. tincture) in a teaspoonful of water, every half hour for 3 or 4 doses.^ If vomiting occurs in spite of preliminary medication and anestheti- zation by proper methods, one of the oldest and simplest methods of re- lief is the inhalation of vinegar fumes. Sometimes it may be necessary to give a rectal injection of 30 to 40 drops of deodorized tincture of opium with 60 grains of sodium, bromid, to quiet the vomiting center. MANAGEMENT OF DIFFICULT OE UNUSUAL CASES In the foregoing pages we have considered the adjuvant manage- ment of ordinary cases — cases in which the course of anesthesia conforms to what, from experience, one may safely predict; cases in which, in other words, the expected happens. The anesthetist, however, who settles himself comfortably at the head of the patient, believing that no dangers need be anticipated so long as he has observed the rules for preliminary medication and so long as he is careful in his technique of administration, is apt at any moment to have a rude awakening, for anesthesia is no exception to the general rule of life, and the unexpected must always be anticipated. This is true (1) *Am. J. Surg., 4, 152. ^ The post-anesthetic treatment varies, of course, with the nature of the oper- ation. 380 ANESTHESIA particularly, because of the fact that individual susceptibility, or insus- ceptibility, to the given agent or method of administration may upset all calculations; (2) because a slight error in technique may convert minor difficulties into those of major proportions; (3) because the exigencies of the surgical procedure itself may create unexpected emergencies for the anesthetist; because latent or undiscovered pathological conditions may become complicating factors. The minor difficulties which may be encountered may be grouped un- der the following heads : (1) Eespiratory; (2) muscular; (3) nervous; (4) idiosyncratic. Eespieatory Dyspnea, hyperpnea, apnea, and stertor are among the respiratory difficulties most commonly encountered. Some patients, particularly young children and nervous women, persist, despite suggestive therapy, in an irregular or hesitating manner of breathing, while others "hold their breath." If allowed to go under the anesthetic in this way, the manner of breathing may characterize the stage of surgical narcosis. In some cases more serious respiratory disturbances, even temporary respira- tory arrest (apnea), may supervene, calling for the more heroic manage- ment discussed hereafter (see p. 393). A too strong vapor (chloroform or ether) may give rise to hesitant breathing after loss of consciousness. As a rule, safe, rhythmical respira- tion can be induced reflexly by the manipulation of the lips (brisk rub- bing with towel or sponge), or fauces (swabbing out with rough gauze), or other form of peripheral stimulation. The convulsive inspiratory effort (sobbing) with contraction of the diaphragm and spasmodic closure of the glottis, particularly noted in children, may lead to unpleasant complications because of the liability to the sudden inhalation of too large quantities of the anesthetic, with consequent asphyxia, or overdose symptoms, varying according to the anesthetic employed. If the anesthesia is begun while the patient is still breathing in this manner, the administrator must be on guard and the anesthetic dose regulated accordingly. If the graver respiratory manifestations present themselves, they must be dealt with as hereinafter indicated. In chloroform narcosis one must always be on guard for so-called false chloroform anesthesia — early shallow breathing instead of aug- mented breathing, which marks the second stage in the uneventful cases. If this be mistaken for a quickly induced surgical narcosis, with com- plete loss of sensation, etc., and the anesthetic be continued and the operation begun as if this were so, the patient may be plunged into pro- found shock, calling for the treatment outlined in this chapter. TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 381 or the error may be recognized and corrected by peripheral stimulation, friction applied to lips, or face, or hypochondriac region, vigorous rub- bing, slapping, or pinching. Sometimes in intranasal surgery, sneezing, of reflex origin, may oc- cur and persist, becoming so violent as to cause a distinct complication. This can usually be controlled by spraying the nasal passages with co- cain. Sneezing, according to Hewitt, may be so violent as to constitute a distinct difficulty, especially in delicate operations about the face.'^ In operations upon the intestines, hiccough, due to some reflex irrita- tion, may become a disturbing factor. If the anesthesia is initiated properly, and care is taken to prevent an accumulation of mucus in the fauces, and hence the swallowing of an undue quantity thereof, this phenomenon is easily controlled. The coughing, retching, and vomiting, minor difficulties arising early in the administration from improper preparation of the patient or from imperfect technique, may become annoying features in the stage of surgi- cal narcosis. Deepening the narcosis will generally obviate these phe- nomena. Muscular Various muscular phenomena have been noted by different observers, aside from the struggling and other manifestations of muscular reflexes which accompany the stage of excitement as ordinarily observed. Tris- mus, or jaw spasm, spasm of the abdominal muscles, general persistent muscular rigidity, fine muscular tremors, such as the "piano playing" movements of chloroform anesthesia, the spasmodic contractions of the pectoral muscles indicating slight asphyxia, are all to be met with in ex- ceptional cases. The various clonic muscular phenomena may become a serious menace to life if mistaken for a return to the second stage of anesthesia (particularly with chloroform). If the narcosis is deepened under this misapprehension, the patient may be quickly and unexpect- edly plunged into the stage of overdose, which may call for vigorous measures of resuscitation. ISTervous In exceptional cases, particularly among neurotic subjects, and when preliminary medication has been neglected, the administration of any inhalation anesthetic may be followed by the immediate onset of vio- lent insanity. If operation is imperative in such cases, it is best to delay the further administration until narcotic medication has had time to take full effect. The anesthetic should then be given very gradually, ^Hewitt: '' Anaesthetics, " 1912, 912, 543; see, also, Lancet, Dec. 2 and 16, 1893. 382 ANESTHESIA beginning with the essence of orange, if an open method is indicated. If a closed method, essence of orange or nitrous oxid. Idiosyncratic It is a well-known fact that some individuals cannot be operated upon under local or spinal analgesia. (See case reported by Bainbridge, p. 623.) So, with inhalation anesthetics, very rare cases of insuscepti- bility, apparent or real, are encountered. Hewitt ^ reports two cases in which there was insusceptibility to nitrous oxid, probably traceable to alcoholism. He directs attention to the point that an acquired suscepti- bility may be manifested in persons infected with malarial parasites. The same author reports two other cases in which there was marked insus- ceptibility. In one the induction was begun with nitrous oxid and ether, with a change to chloroform, then to ether, the C. E. mixture finally proving successful. In the other case the anesthetic was begun with ether by the open method, without preliminary medication. After wait- ing for morphin and atropin to take effect, another effort was made, be- ginning with chloroform and switching to ether. Loud crowing breath- ing lasted throughout, but the operation was completed successfully. Hypersensitiveness, rather than insusceptibility, it would seem, is the difficulty to be guarded against. There are practically no minor difficulties of any unusual character encountered after anesthesia. Among the major difficulties which may be encountered in the course of inhalation anesthesia, or the after-management of the case, and which directly concern the anesthetist, are (1) shock, and (2) post-anesthetic toxemia. These difficulties undoubtedly vary with the anesthetic, with the gen- eral preliminary and concurrent management of the case, with the method of administration, with the physical peculiarities of the patient, with the technique and skill employed by the surgeon, and with preexist- ent pathological conditions. Whatever the cause or causes, and however these complications may be precipitated, the anesthetist must know how best and most expedi- tiously to deal with them. They are, therefore, directly concerned with the prognosis and treatment of the individual case, and it behooves the anesthetist to be familiar with them from the theoretical, as well as from the practical, point of view. In the pages which follow, an attempt is made to set forth, as briefly as possible, the theories, and the views with regard to management, of those who, by virtue of their original observations, are best qualified to speak with authority. Whatever per- ^ Hewitt: "Anaesthetics," 1912, 332, 333; 548, 549. TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 383 sonal experience the authors have had is merely corroborative; we there- fore take the liberty of drawing freely from those who have concentrated effort in these given directions. Shock By far the most important complication which may arise in the clinical experience of the anesthetist is shock. When, for any reason, the patient emerges from the even plane of a safe and satisfactory anes- thesia into that alarming composite condition which is designated as shock, the anesthetist must be able quickly to marshal all his resources toward the restoration of the normal anesthetic condition. Shock may be considered under the four heads, according to the chief factors which induce it, of : ( 1 ) surgical shock, that for which the sur- geon is responsible; (2) psychic shock, shock produced in a patient by inability to control the nervous system; (3) dietetic shock; (4) anes- thetic shock, that for which the anesthetist is responsible. Surgical Shock. — Shock has been described ^ as "a condition of gen- eral depression produced by various causes." With shock we have: (1) a fall ill blood pressure; (2) nerve centers react feebly to afferent stim- uli; (3) pulse rapid and feeble; (4) respiration shallow; (5) all cu- taneous reflexes lessened; (6) increased perspiration, with skin cold and moist ; . ( 7 ) temperature lowered ; ( 8 ) mental condition one of quiet depression, patient may be conscious [this, of course, does not apply to shock during anesthesia] ; (9) no pain or discomfort, but a feeling of weakness. Various factors are concerned in the production of shock, and may pertain as much to the shock produced by surgical procedure, during narcosis, as when shock is the result of accident or any cause operative under ordinary circumstances. Keen ^ gives these factors as follows : "Age. — In the new-born, before the physiological connections be- tween the great divisions of the central nervous system have been estab- lished, it is quite probable that at least certain operations are very much more nearly shock-free than they will ever be again. (There is a short period of immunity that disappears with the establishment of the through paths of the nervous system). They are not only shock-free, but free from any appreciation of pain: In the new-born extensive operations for cleft palate are endured without anesthesia, pain, or shock, the only immediate risk being hemorrhage. Within a week or more these physiological connections become established, after which the infant becomes even more susceptible to shock than the adult. ^ ' ' American Practice of Surgery, " 1, A 83. ''Keen's "Surgery," I, 922. 384 ANESTHESIA "Adult Life. — This is the period of greatest resistan^^e to shock. "Old Age. — The senile heart has an uncertain and limited range of action. The arteries are hard and the blood pressure is high. The aged only apparently endure operations well. The risk is determined not by the age of the patient, but the age of the circulatory apparatus. Toward the completion of life's cycle the resistance to shock is at a minimum. "Time of Day. — The vital powers are higliest in the morning, and the psychic factor at a minimum. The most unfavorable time 12 to 2 A. M. Autumn and early winter the hest. Summer the worst. "Occupation. — Professional and business men are more susceptible than the farmer, laborer, and mechanic. The industrious are better sub- jects than the idle. The resistance of criminals is remarkable. Soldiers and sailors are good risks; athletes, not so good; worst risk, overworked surgeon over 50 years of age. Cachectic patients bear operations poorly. In pernicious anemia the operator's risk is great. In chronic anemia the risk is better, but still great. In chronic anemia from loss of blood the risk is better; in acute anemia from hemorrhage the risk is still better.'^ Psychic Shock. — Psychic shock is "due to the poiverful impulses from the highly specialized centers of the cerebrum acting upon the vital cen- ters of the medulla." , , It is hard to differentiate between prostration by fear and prostration by injury. In most injuries the psychic and mechanical factors are mixed. "The deep impression left upon the brain by a powerful nervous shock often endures for months and years." Ieritating Chemicals. — Those which cause marked irritation at the point of contact may produce shock. (According to Mummery, "Burns of the first and second degree with extreme irritation only are apt to cause more shock than burns of the third and fourth degree causing destruction of tissue." Burns extend- ing over half of the body frequently cause death from shock.) Toxic Causes. — Abscess breaking into the peritoneal cavity, and pouring out intensely irritating chemical compounds, causes shock by intense local irritation and constitutional disturbance. Mechanical Causes. — By mechanical stimulation of nerve centers or trauma afferent impulses are sent toward the centers. "An abnormally low Hood pressure is the essential phenomenon of the state commonly designated svirgical shock." "Shock is the problem of the various kinds of stimulation of the nervous system." Susceptibility of the various tissues depends upon the quality and quantity of their nerve supply. "A fall in blood pressure usually occurs while incising the skin over the abdomen." TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 385 "Asphyxia is always attended by a retarded pulse and slow and pow- erful respiratory efforts. A fall in temperature is the result of low Mood pressure." Circulation. — The entire arterial system bleeds into the dilated venous system, and the bulk of the blood is not freely circulated. Eespiration. — It is accelerated. Sighing and irregular or increased action may appear. The respiration wave is shortened. Inspiratory and expiratory efforts are quickened, and the pause is lengthened. Later, the gasping type of respiration with tracheal and chin tug indicates im- pending dissolution. Muscular System. — The voluntary and involuntary muscular sys- tems are relaxed; kidney and digestive tract diminished in function; skin relaxes; pallor with consequent outflow of water or perspiration. Face is shrunken, pinched, and elongated; eyes lusterless and sunken, with lids only half closed; lips parted, thin, and pale, but may be cy- anotic; drooping jaw, partly open mouth, falling in of cheeks. Crile,^ in his epoch-making experimental researches concerning shock, made the following observations concerning its production and the re- sultant effects. These observations were made upon animals in the laboratory. "Skin. — Cutting and tearing caused in the greater number of instances a rise of blood pressure, though sometimes no effect was ob- served. "Negative Eesults. — Kidney, Spleen, Bladder, Eyes. — Mechanical injury caused usually no appreciable change in either the circulation or the respiration. "Ears. — As skin usually. "Mouth. — Crushing, tearing, cutting, and puncturing the tongue produced no effect on either the circulation or respiration. "Heart. — The slightest direct contact with the heart caused marked changes in its beat and in the blood pressure, — a fall in blood pressure, with short, irregular strokes. "Diaphragm. — Contact, however slight, with the abdominal side of the diaphragm caused in every instance markedly arhythmic respiration. "Ahdomen. — In making the incision through the skin in the abdom- inal sections there was frequently noted a fall in the blood pressure ; this, in fact, was the rule. "Cutting muscles or fascia produced little or no effect. On opening the peritoneum a fall was noted. ''Liver. — Manipulation of the gall-bladder caused a marked tem- porary fall. "Uterus. — A rise in blood pressure. "Testicles. — A fall in blood pressure. ' Crile, George W. : "An Experimental Eesearch into Surgical Shock." 386 ANESTHESIA "Penis. — A fall in blood pressure. "Vagina. — A rise in blood pressure, and increase in depth and fre- quency of the respirations. "Anus. — Same. "Peritoneum. — Contact, however slight, with the peritoneum or vis- ceral peritoiieum caused marked arhythmic respiratory action. The diaphragmatic peritoneum produced the most marked respiratory changes. Continuation of the manij)ulation does not secure tolerance un- less confined to the same area." The duration of an operation was found to be an important factor in the production of shock. Animals may be killed by the effect of con- tinuous anesthesia alone, though the anesthetic is carefully administered, so that a percentage — calculated upon the ratio between the actual dura- tion of anesthesia and the average length of time a dog may survive continuous anesthesia, — is allowed for the pure anesthetic factor in any given case ; that is to say, if ten hours be allowed as the average length of time a dog may live under continuous anesthesia and the given experi- ment lasted two hours, then twenty per cent of the cause of death was cal- culated to represent the anesthetic factor. This calculation applies to ether. There is strong evidence tending to show that chloroform, even barring accidents, is a more potent factor in destroying the animal than is ether. Contact with air is a very great irritant to local tissues, owing to the lowering of local temperature and to the drying. Exposure of the thoracic cavity causes great disturbance of respiration, and the time of exposure should be as short as possible. "The element of time in ab- dominal operations in every experiment was unmistakable." Temperature. — The effect on the intestines of cold water and of the intravenous cold saline solution showed more directly the depressing in- fluences of the cold. The direct effect of warm towels applied to the ex- posed intestines, of warm saline in the abdomen, improved the respira- tion immediately, and as nearly as could be estimated caused at least a check in the declining blood pressure. Anesthesia. — The respirations in over-anesthesia became generally more shallow and slower, and if the anesthetic was continued would fail suddenly. The blood pressure pari passu gradually fell. Upon removing the ether both would rise, much as they fell. The respiratory indica- tions were usually in advance of any other symptom in foretelling the tendency of the anesthesia. The effect upon respiration was so constantly in advance of other effects, for example, that upon the circulation, that the latter was habitually neglected. Ether in no instance caused sudden cardiac arrest ; chloroform, three times, each time early in the in- halation and before surgical anesthesia had been induced. Chloroform proved to be more toxic than ether. Over-anesthesia rendered the ani- TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 387 mals subject to early collapse and decidedly less capable of withstanding a protracted experiment. Hemor7-hage. — Loss of blood always predisposes to shock. Eespira- tions are always accelerated and deepened in profuse hemorrhage. Hemorrhage from the large venous trunks caused the most pro- found effect upon the blood pressure, because the quantity of blood supplied to the heart was immediately diminished, while if the hemorrhage was arterial the income of. blood was not so suddenly diminished.^ Dietetic Shock. — Chauvin and fficonomos ^ state that disturbances of metabolism are observed regardless of the anesthetic, or method of ad- ministration, whether local, spinal, or general. This "dietetic shock" is due to fasting immediately preliminary to and following anesthesia. This shock can be avoided by the use of glucose, 150 gm., tincture of cinna- mon, 6 gm., and tincture of nux vomica, 0.59 gm. and water to make 300 gm., or some other easily digested carbohydrate diet. When this mixture was taken the day before and the three days following the operation, the urine showed no pathologic changes such as occurred when this regime was not followed. Anesthetic Shock. — In the preceding pages we have discussed shock from the surgical and theoretical points of view. We come now to the consideration of shock caused by the anesthetist,^ independently of the ^According to J. Am. Med. Assn., June 14, 1913, in post-partum hemorrhage the patient may survive a loss of about half of the total amount of the blood in the body. Whether or not this conclusion is applicable to other forms of acute loss of blood is not definitely determined, but it is probably not far out of the way. ^Chauvin, E., and CEconomos, S. N. : "Necessity for Avoiding Dietetic Shock in Operative Cases," Bevue de Chir., Paris, Mar., 33, No. 3. ^ Shock, hemorrhage, and the anesthetic are closely related, according to French: "In the testing work in anesthesia the writer has had foremost in mind the great need of reducing shock. It is generally conceded that the child is more susceptible to shock than the adult, due, in some way, no doubt, to the fact that the child is anatomically and physiologically different from the adult. The tests have, therefore, been applied especially to children in the controlling of hemorrhage and in the administration of anesthetics. We find no variance from the belief among surgeons who have given careful thought to their work upon infants and children, that the losing of blood is a matter of the greatest import to them and that all means should be used to prevent hemorrhage in operating upon them. And we are now convinced that shock from the loss of blood and from the anesthetic can be materially reduced by the manner of admin- istering the anesthetic. ' ' According to the observations of the writer of this paper there is, irrespec- tive of all other conditions, a well defined and never failing relationship between the degree of skill in which a patient is anesthetized in the upright position and the amount of hemorrhage which occurs during the anesthesia, for there seems to be no question but that hemorrhage is reduced if the anesthetic, from the be- ginning, is smoothly administered, the second stage omitted, and the patient 388 ANESTHESIA surgical procedure The subject is partly covered in the discussion of the fourth stage, or the stage of overdose, of each of the inhalation anesthetic agents. Other factors, however, besides overdose, may enter into the production of anesthetic shock. These, together with the treatment of the condition, however it may be produced, are considered in the fol- lowing pages. Anesthetic shock may be produced in three ways: (1) By giving an overdose of the anesthetic; (2) by maintaining too light an anes- thesia; (3) by failing to keep an open airway. We will discuss these briefly, seriatim. Shock Caused by Giving aist Overdose of the Anesthetic. — It has been stated that the liability of shock from an overdose of the anes- thetic varies with the subject, with the method of administration, with the agent employed, and with various other factors. The signs of over- dose have been given under each inhalation anesthetic, respectively, and need not be reiterated here. With nitrous oxid, if a slight degree of asphyxia, by delimiting the supply of air or oxygen, is maintained throughout a long operation, this, in itself, is apt to produce a state of shock. This is all the more apt to occur if a certain amount of shock has been caused through the manipu- lation of the surgeon, or through hemorrhage. This combination of circumstances may lead to complete shock, calling for the measures of resuscitation described under Surgical Shock, provided the im- mediate withdrawal of the anesthetic and the restoration of carbon dioxid balance, in accordance with the theory of Henderson, are not sufficient to restore respiration and circulation to a plane of safety. With ether the chief danger of shock from an overdose is caused by the maintenance of too deep an anesthesia during a long and difficult operation. Such a state of affairs always calls, primarily, for lightening the anesthesia. If this is not sufficient, other methods described else- where should be employed. With ethyl chlorid it is to be remembered that shock from overdose is especially liable to occur with a careless or inexperienced adminis- trator, for the reason that anesthesia is so rapidly induced that the brought into full surgical anesthesia without jarring or body disturbance of any kind. The uniform employment of helpful mental suggestion by every in- dividual in contact with the patient up to the time of the induction of anesthesia, to assist in preventing an excessive discharge of nervous energy through fear — which is one of the elements in the ' anoci-association ' of Crile ; the administra- tion of morphin to patients who display a marked degree of apprehension; an anesthetizing room free from an atmosphere of excitement and from unneces- sary noise ; the preliminary use of nitrous oxid or the essence of orange. ' ' French, Thomas E. : "Nitrous Oxid, Essence of Orange, Ether and Sequestra- tion in General Anesthesia." N. Y. Med. J., May 24, 1913. TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 389 border line between safety and danger may be quite easily passed. This is particularly true because of the fall in blood pressure which always accompanies anesthesia by this agent. In the presence of the signs of shock already stated, if immediate withdrawal of the anesthetic does not revive the patient, the more active measures must be quickly insti- tuted. With cidoroform it is more dangerous to keep the patient under deep surgical anesthesia than with any other agent, except, perhaps, ethyl chlorid. The shallow respiration, weak, thready pulse, sudden and com- plete dilatation of the pupil, and extreme pallor of the face are the danger signals which, separately or combined, should put the anes- thetist on his guard. At times the anesthetic, in conjunction with the surgical iDrocedure, brings about a condition of shock with start- ling suddenness. Withdrawal of the anesthetic may answer the pur- pose, but it is more than probable that more heroic measures will be necessary. Shock During Light Anesthesia. — This form of shock is espe- cially seen during laparotomies in which the patient has been too hastily or improj)erly anesthetized and the surgeon begins the operation before full surgical anesthesia is reached. We will suppose the patient just beyond the second stage, but not in full surgical anesthesia. In this condition, if the operation is a lapa- rotomy, every tng upon the viscera will increase the respiratory effort. If this hyperpnea is kept up during the entire period and the operation is a lengthy one, it will result in acapnia, and thus finally affect the circu- lation. If the patient is already in a reduced condition there is a possibility, of this condition being a serious one. If the operation is upon an extremity, where no important vessels or nerves are involved, the chances for a dangerous degree of shock are ma- terially lessened. Shock from an Obstructed Airway. — The space between the ex- ternal respiratory orifices and the epiglottis has been very properly called by Meltzer the "death space," inasmuch as this part of the respiratory tract causes more trouble to the anesthetist than everything else com- bined. Shock may be caused from allowing a slight degree of cyanosis throughout a long operation, this being caused by allowing a more or less continuous interruption to the breathing. Shock is more often caused in this way than is commonly supposed. Obstruction hy Closure of the Alee of the Nose. — In elderly people especially, or in very weak or nervous individuals, obstruction of the air passages by closure of the alse is not an unusual thing. It is easily pre- vented by placing rubber tubing of convenient size, about an inch and a 390 ANESTHESIA half long, in each nostril, allowing the ends to project a quarter to half an inch outside. This condition may also be remedied by manipulating the lower jaw in such a way that the patient is compelled to breathe through the mouth instead of the nose. Shock from Labial Stertor. — A dangerous degree of shock from this source is not apt to occur because this form of stertor is so objectionably apparent to all present that it is usually quickly remedied if the open method is in use. It may cause serious trou^ble if the closed method is being used and the anesthetist is unable to observe the lips of the pa- tient. This condition is modified by pressing the jaw upward and at the same time slightly forward. Also by placing the end of a towel or a piece of gauze between the lips. Closure of the Glottis by the Tongue Dropping Back. — This is the most common form of stertor met with, and is fortunately remedied very easily. It is caused by the relaxation of the muscles supporting the tongue as the patient reaches the third stage of anesthesia. The tongue drops back, thus closing or partially closing the glottis. Tongue stertor may be caused in the beginning of the anesthesia by failure of the anes- thetist to remove the pillow, or anything that may be under the patient's head, or by allowing the head to remain in a straight line with the body, instead of having it turned either to the right or left side. There are a small number of patients who breathe better when the head is propped up and the chin pressed in, but these are the exceptions. The vast ma- jority of patients breathe much better in full surgical anesthesia with the head on the same horizontal plane with the body, and also turned slightly to one side. This does not apply to obese patients with a short neck. These patients' heads should be supported in such a way that no "effort is thrown upon the neck muscles. Respirations. — If a patient's respirations are perceptibly increased or interfered with by a closed method, and it is impossible to maintain an even anesthesia in this way, a change to the open method should imme- diately be made. Many anesthetists use an artificial airway during surgical anesthesia. Ferguson's description of the original Hewitt's airway and his own fol- lows: "Hewitt's airway (Fig. 138) consists of a somewhat rigid rubber tube, C, curved so that, when it is in position in the patient's mouth, it will conform to the upper aspect of the base of the tongue. It has its laryngeal end beveled to correspond with the opening into the larynx. At the proximal end a metal funnel-shaped mouthpiece is attached. Figure 138 B. This has a deep groove so as to enable it to be clutched by the teeth in order to hold it in position. The tube is introduced into the pharynx and respiration takes place through it. TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 391 Fig. 138. — Hewitt's Artificial Airway. "Fer^ison's modification of Sir Frederick Hewitt's airway, Figure 139, differs from its predecessor in having tlie proximal end of the funnel closed (Fig. 139, D) aud two openings (one on each side of the truncated cone) for the ingress and egress of air, Figure 139, E. Thus there can be no danger of dropping ether into the top of the funnel, because it is not open, and since the orifices are in the sides which slope toward the lumen of the tube, and therefore away from the source of dropping, it is almost impossible to get any ether into the tube. Should the patient's cheek be resting on the table, any ether that might enter the upper fenestra would pass across the funnel and out of the lower fenestra, so that it is almost impossible for any liquid ether to enter the airway, no matter what the position of the patient may be. "Ferguson lengthened and otherwise changed the metal thimble (Fig. 138, F) so that it extends well into the rubber tube C Avithout enlarging the middle of the tube (Fig. 139, G). Consequently a patient's teeth may clutch the rubber tube C anywhere between G and the groove near E (Fig. 139) and the inside metal tube will re- sist the pressure and the lu- men of the airway remain open. "This airway should be in- troduced after surgical anes- thesia has been reached. If the patient is not well under the anesthetic, the contact of the tube with the pharyngeal wall may incite gagging. To adjust the airway the jaws should be separated, the tongue brought gently for- ward, and the airway passed back into the pharynx with the convex portion of the curved rubber tube nearest the roof of the mouth. The instrument of itself will then assume a proper position. Fig. 139. — Ferguson's Modification of Hewitt's Artificial Airway. 392 ANESTHESIA The pharyngeal tube is useful to do away with respiratory embarrass- ment due to any form of occlusion of the extrapharyngeal respiratory tract." 1 Connell's Breatlimg Tube. — Connell's breathing tube (Fig. 140) is a flattened copper tube curved to fit the roof of the mouth, easy of in- troduction. It provides for the minimum displaceinent of oral struc- tures and abundant free gas channel from the outer world to the lower pharynx. This tube is used in ordinary anesthesia with any face mask. An attachment at the end of this tube permits the placing of a re- breathing bag fitted with a stopcock at the distal end. Rebreathing may be regulated by this stopcock. A rubber dam is placed on this pharyn- geal tube and so adjusted between the gums and lips as to make an air= tight joint. Fig. 140. — Connell's Breathing Tube. A flattened metallic tube curved to fit the palate and pharynx. Provides a free non-collapsible airway without dis- placement of oral structures. With the placing of any breathing tubes, or the maintenance of a free airway by other methods, the stertor due to the anesthetic is eliminated. Treatment of Anesthetic Shock." — When the pulse disappears and the respirations become very shallow or cease, in the absence of cause for suspecting surgical shock, the anesthetist may know that ho is to blame for the condition. He must be able to quickly judge the par- ticular error of technique which has brought about the state of shock, and to correct this error accordingly. If withdraAving the anesthetic, deepen- ing the narcosis, or restoring openness of airway fail to revive the pa- tient, certain other measures must be resorted to, according to the sever- ity of the shock. (1) A quick, vigorous slap on the chest; (2) imme- diate lowering of the head. If the subject is an infant, it should be suspended by the heels; (3) dilatation of the sphincter ani; (4) ^J. Am. Med. Assn., June 14, 1913. ^For Eesuscitation by Electricity, see Chapter XVI. TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 393 the application of hoi or cold cloths to the face. \i these simpler measures do not suffice; one must resort to (5) artificial respiration. This is accomplished hy various methods, some of which are given below. Artificial Respiration hy Manual Means. — (1) The anesthetist grasps the arms of the patient near the elbows, and presses them firmly against the sides, thus expelling any chloroform vapor that may be in the air passages. The arms should be held tightly against the patient's sides for at least fifteen seconds. (3) They should then be drawn laterally below the head and held in this position for ten or fifteen seconds. This procedure should be repeated fifteen times a minute. Massage of tlie precordial region by an assistant is most helpful, as is also intermittent dilatation of the sphincter. Hypodermics do little, if any, good at this time. It is the anesthetist's duty to see that an open airway is maintained during this procedure. The mouth gag should be inserted and the tongue forceps applied, and the tongue pulled well for- ward, if there is any occlu- sion of the air passages. Traction of the tongue sometimes stimulates the respiration. (3) If none of these efl^orts is successful and the patient is in a state of collapse, the following method of Lewis ^ should be tried: Lewis "P en clulum Swing." — "The patient should be suspended by the fully flexed knees and swung forcibly from side to side for a period of from one to two minutes. Suspension is best accomplished by the operator's forearms so grasping the patient's knees as to hold the anterior surface of both legs against operator's chest, allowing dependence of thighs, trunk, arms, and head of patient, facing away from operator. Except in children it is necessary for the operator to stand upon a dais, box, or chair of sufficient height to permit full pendulum swing of the patient from side to side without contact of patient's arms or head with the floor. Swinging should be done as vigorously as possible to secure by centrifugation a ^ Lewis, Eugene Richards: In a private communication. Fig. 141. — The Lewis Pendulum Sw^ng. 394 ANESTHESIA forcible distention of heart and intracranial vessels. The suffusion of neck and face which is brought on by this swinging is the index by which to judge the effect of centrifugation. Notes on several cases follow. "September 1, 1899, male, 15 years, brought to Wilkes-Barre City Hospital with dislocation of right femur, 20 hours' standing. Physical examination negative ; chloroform was administered ; patient resisted con- siderably and suddenly ceased breathing. Usual measures and artificial respiration continuously for over ten minutes, during which time strych- nin and atropin were administered hypodermically, but failed to re- establish respiration. We then attempted to restore the patient by in- creasing the volume of blood in head, neck, and chest, using forcible centrifugation to accomplish this. Accordingly the patient was grasped by the knees, and was swung to and fro, sideways with all possible force, until there was manifest a deep suffusion upon neck and head. The patient was then placed upon the table, and was found to be breathing spontaneously. Chloroform was continued cautiously, and reduction of the dislocation was effected. "In July, 1901, at Wills Eye Hospital, Philadelphia, service of Dr. Eadcliffe, case for squint operation. Chloroform was given, with early collapse and cessation of respiration. Slapping chest, cold douching, atropin, and strychnin hypodermically and artificial respiration all failed to restore breathing. After about four minutes, patient was swung as above described, until marked suffusion of face and neck occurred ; spon- taneous respiration was reestablished. "Trinity Hospital, Milwaukee, service of H. V. Wurdemann, Jan- uary 28, 1902, Patterson, medical student, 22 years, for brossage of lids and canthoplasty. Physical examination negative. Chloroform anesthesia, collapse and cessation of respiration before beginning of operation. After three minutes of ineffectual attempts to revive the patient, he was swung vigorously till face and neck were well suffused, resulting in establishing spontaneous respiration. Operation was thereupon completed under chloroform anesthesia without further trouble. "In 1903 or 1904 chloroform was given in a case of tonsillect- omy. Collapse occurred and respiration ceased. Douching, slapping chest, stretching sphincter ani and artificial respiration for four or fi.ve minutes failed to revive patient. Swinging for about 45 sec- onds succeeded in establishing spontaneous respiration without further trouble. "March 29, 1911, Max L., 8 years, brought to Mercy Hospital from Wisconsin. Hypertrophic tonsils and adenoids. Physical examination negative. Chloroform was given, patient somewhat nervous, but resisted very little. Early in narcosis, before loss of all reflexes, patient's respira- TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 395 tion suddenly l)ecame superficial and then stopped entirely. Very slight grade of cyanosis followed by a sudden marked pallor with radial and Fig. 142 a. — Artificial Respiration. First Movement. temporal pulse not palpable; widely dilated pupils. Artifical respira- tion with lowered head was ineffective. Dilating sphincter gave no re- FiG. 142 B. — Artificial Respiration. Second Movement. sponse whatever. Amyl nitrite was useless because patient's respiration had ceased. The patient was now grasped under flexed knees and swung 396 ANESTHESIA from side to side with considerable force, much the same as one might swing an asphyxia livida at birth. A pale cyanosis soon appeared about the mouth; respiratory movements, at first shallow and irregular, could be made out, and soon spontaneous respiration was established. The force of the heart beats remained irregular for at least an hour, and a circumoral pallor was present for at least two hours. The operation was performed the following day, ether as anesthetic, with no return of symp- toms of day before. "April 19, 1911. Well-built girl of 24 years, weight about 150 pounds. Chloroform as anesthetic. Did not struggle, but refused to breathe anesthetic quietly and regularly. Had reached a deeper stage of narcosis than preceding patient. Failure of respiration came on sud- denly, but pulse remained fair. Cyanosis became marked. Artificial respiration, camphorated oil, ammonia hypodermically, with stretching of sphincter ani failed. Eesuscitation was now attempted by swinging the 150-pound patient as above described. Since this was primarily and entirely respiratory failure, the reaction following suspension and swing- ing was all the more marked. The operation Avas sucessfully completed with ether, after resuscitation." Apparatus for the Induction of Artificial Respiration. — It cannot be too strongly emphasized that, no matter how efficient may be a given apparatus for the maintenance of artificdal respiration, when the exi- gency arises no time must be lost while the apparatus is being put in place. It is necessary, therefore, to resort to one or more of the meas- ures for the induction of artificial respiration described in the foregoing pages, while the mask is being placed upon the face, or the tubes into the pharynx or trachea, as the case may be. JSTor should such measures be discontinued until the apparatus is working — in other words, until air is being forced into the lungs. Draeger's Pulmotor. — The Draeger pulmotor is being used with great success. It will not overdistend a small lung, und will fully dis- tend the adult lung. It works automatically, adapting itself to the ca- pacity of the lung. The dif- ferent parts, and V 9-f/ the manner of application, are illustrated and explained in the =^ c. "^'^Jpj 1 ""ts h a c CO mpanying figures. Preliminaries. — ■"" — --- 1. Eemove the Fig. 143a. clothing from TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 397 Fig. 143b. Fig. 143c. the upper part of the patient's body. In cases of drowning, lay the patient face downward, on a support that raises the abdomen, and apply pres- sure to the back so as to make the water rush out of the lungs and stomach. 2, Free, the mouth and throat from mucus, preferably by means of a cloth wrapped round the forefinger. 3. The unconscious patient should be laid on his back, and the- shoulders raised by means of a folded garment, leaving the head well thrown back. 4. To enable the air to gain free ac- cess to the lungs, the tongue should be gripped with the forceps provided for that purpose, and then draAvn forward as far as it will come, and held in that position. Placing the Pulmotor in Position. — 5. The pul- motor mask must be buckled firmly to the head, leaving the tongue projecting between the lower jaw and the edge of the mask. The flexible tubes should rest on the forehead, not over the mouth. Take care that the mask fits airtight. This can be accomplished by bending the edge of the mask and tightening its two straps. The lower jaw must not be forced back (down- ward). If necessary, it should be pushed forward, by means of the manipulation illustrated in Figure 143D, to such an extent that the teeth in the lower jaw project beyond those of the upper jaw, not forget- ting to keep the tongue firmly drawn out. 6. The lever U of the ap- paratus should be moved into the position marked "Pul- motor," and the valve of the oxygen cylinder V opened. If the passage to the lungs is open, and the mask fits air- tight, respiration will com- FiG. 143e. mence. Fig. 143d. 398 ANESTHESIA Fig. 143f. If this does not occur, and the apparatus is found to reverse too quickly, and to continue doing so, it is a sign that the passage to the lungs is not free. In such event, remove the mucus, draw the tongue further out and push the lovs^er jaw for- ward. If the apparatus does not reverse at all, then the mask is not fitting tight. (See 5.) If necessary, the pulmotor can be made to pulsate (delivery and suc- tion strokes) by hand. (See 8.) The Pulmotor in Operatio n. — 7. The air forced in and out of the body by the pulmotor should pass only into Fig. 143g. the lungs, and not into the stomach. In order to insure this and to close the esophagus, the manipulation devised by Dr. Eoth Fig. 143h. Fig. 143i. TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 39'J of Liibeck, consisting in the application of finger pressure to the Adam's apple of the throat, is practiced. Two fingers are gently pressed on the middle of the throat against the windpipe, Avhich, being firm, closes the underlying esophagus, and thus completely prevents access to the stomach. Fig. 143j. 8. If, from any cause, respiration should not go on automatically, the pulmotor may be reversed by hand, by moving the small lever H to and fro, the lever being firmly held all the time. The Lungmotor. — T he _ lungmotor is a device operated by hand, with notched grada- tions for different ages, as shown in Fig. 144. It does not depend upon back pressure in the lungs, but exhausts the air upon expiration. The advan- tages claimed for it are that it requires less physical labor than manual methods, and de- livers a positive volume of air with each movement. It is available for persons of all ages and correspondingly vary- ing lung capacities. Meltzers Devices for Arti- ficial Respiration.^ — Meltzer has evolved two methods for the induction of artificial respiration : Pharyngeal tube; (2) mask, as in other devices. In either case > J. Am. Med. Assn., May 10, 1913, 1407. Fig. 144. — The Lungmotor. (1) the Fig. 145. — Meltzer's Apparatus for Artificial Respiration with Pharyngeal Tube and Foot Bellows. P. T., pharyngeal tube; R. V., respiratory valve. The ling turns the valve; turning to the right (facing the pharyngeal tube) brings an in- spiration and to the left brings an expiration. B., foot-bellows; S. V., safety-valve. The bottle of the safety-valve should be shorter and have a wider diameter than the one in the figure; it is less likely to turn over. S. T., stomach-tube introduced through the opening in the pharyngeal tube. Fig. 146. — ^Meltzer's Apparatus foe Artificial Respiration with Mask Attached to Oxygen Tank. M., mask; Infl., tube for inflating the rubber ring around the rim of the mask; R. V., respiratory valve; S. V., safety-valve. An oxygen cylinder provides here the insufflation pressure. The figure shows also the weight on the abdo- men and the belt around it. TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 401 apparatus is operated by means of foot bellows, compressed air or oxygen from a tank, or a motor. Figs. 145 and 146 illustrate clearly the mechanism and application of these devices. Meltzer demonstrated that the blood pressure is considerably raised by placing weights upon the abdomen, thus greatly increasing the proba- bility of a successful termination of the efforts at resuscitation. "The weight of the abdomen prevents the entrance of air in any con- siderable quantity into the stomach, and the little which gets there es- capes again when the insufflation is cut off; it never gets into the intes- FiG. 147. — Blood-Pressure Tracing from an Etherized Dog Which Received an Intravenous Injection of Sodium Nitrite. Blood-pressure low, 44 millimeters; pressure on the abdomen brings up the blood pressure to 70 millimeters mercury, and the pulse pressure is nearly doubled in size. tines. The pressure on the abdomen has still another significance. In patients with completely abolished respiration usually the blood pressure is also very low, and most of the blood may be accumulated in the ab- dominal viscera. The heart is then scantily filled, and not enough ar- terial blood is sent to peripheral organs. Under such circumstances a good pressure on the abdomen may raise the blood pressure by even as much as 30 millimeters of mercury; the heart is filled more efficiently, and sends more blood to the medulla oblongata, arousing there the activi- ties of the respiratory and vasomotor centers." Figure 147 shows the effect of abdominal pressure on the blood pressure. Theories Concerning the Cause of Shock. — The theories concerning the cause of shock, however produced, whether by the anesthetic or by the surgical procedure, have come to be accepted as falling under two heads : (1) Crile's theory of deoxygenation, or paralysis of the vasomotor centers, with a "manifest transference of the blood from the arteries into the veins." (2) Henderson's acapnia theory, or the hyperactivity of the vaso- 402 ANESTHESIA motor centers through loss of carbon dioxid from the tissues and the cir- culating blood. Vasomotor Paralysis (Deoxygenation) — Crile. — The phe- nomena of shock, according to this theory, are due to the exhaustion of the vasomotor centers in the medulla and spinal cord, with the resultant loss of control of the pressure of the blood in the arterial system and the consequent collection of the blood in the great splanchnic reservoir in the abdomen. The fall in blood pressure which follows this loss of control is accompanied by a fall in the general body temperature; the respirations become weak from secondary exhaustion of the respiratory centers, the blood and tissues are not properly oxygenated, and the oxy- gen starvation described heretofore (see p. 97), if not checked, leads to loss of consciousness and eventual paralysis of all vital functions and death. This theory of shock is accepted by Mummery, Latham, and English, and a number of others. Prevention of Shock {Crile). — Prevent as far as possible the loss of blood. Atropin, hypodermically administered, was an efficient protec- tion against cardiac inhibition in operations in the "inhibition area" in the larynx, and in such operations as might cause mechanical stimula- tion of the vagi. Cocain, hypodermically injected, guards the heart against cardiac inhibition almost as efficiently as does atropin. "For morphin and alcohol, our observations were negative." Tearing, manip- ulating, stretching, forced dissection, all tend to produce shock, more than the use of sharp instruments and gentle manipulation. "Animals to which, while inducing anesthesia, an overdose had been given did not endure a prolonged experiment, and not only was it more difficult to maintain an even anesthesia afterward, but the animal also showed a marked tendency to recurring respiratory failures." So far as could be judged, less shock was produced when warm so- lutions were used than when cold; when the laboratory was warm, than when near the freezing point. Moist heat ^ protecting the tissues lessened the amount of local irri- tation, and hence the shock. Posture. — Posture is of considerable importance. The blood pressure always rose when the head was tilted dowuAvard, and fell when the board was tilted in the opposite direction. Operations upon the extremities, if performed bloodlessly, and if the nerve trunks had been subjected to a cocain "block," produced no shock. Amputation of a leg caused no more effect than did cutting the hair. In rough axillary and chest dissections there was a marked tendency to respiratory failure. In abdominal procedure, if the omentum was made ^ See Chapter on General Physiology (Warming the Anesthetic; The Utili- zation of Moisture). TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 403 to cover the viscera, thereby preventing direct contact with them, there was very much less shock. Handling the omentum did not produce vasomotor and respiratory disturbance. Dragging in the mesentery was followed by a decline in blood pressure. In operations upon the gall- bladder and liver it was necessary to be cautious as to traction on account of the great fluctuation in blood pressure likely to be caused by mechani- cal interference with the larger venous trunks. The most dangerous area is in the region of the duodenum, pylorus, and gall-bladder. The least dangerous area is the pelvic peritoneum and its viscera. The uterus, tubes, and ovaries contribute but little to shock, even when they are se- verely crushed and torn. The severity of shock induced in abdominal operations is in direct ratio to the distance from the pelvis. Injuries of the large intestines produce much less depression of the blood pressure than those of the small intestines; injuries of the stomach about the same as the small intestines. Intravenous infusion of normal saline solution causes all the blood pressures to rise. Quantities up to twice the amount of blood calculated to be in the animal have been given before the pressure was sustained. The value of these injections is apparently wholly mechanical. The combination of small and frequently repeated hypodermic injections of strychnin, together with saline infusion, produces a sustained effect. Overstimulation was followed later by a greater depression. The appli- cation of heat was of benefit. Treatment of Shock in Accordance with the Vasomotor Paralysis or Deoxygenation Theory. — Naturally, if one accepts the theory of shock proposed by Crile, the treatment must be carried out accordingly. Crile recommends the use of strychnin sulphate and artificial respiration; in other words, an increase in the supply of oxygen. Latham and English ^ advocate the following measures : "The prin- cipal factor in treating shock is to maintain an efficient circulation until such time as the vasomotor centers have recovered, and at the same time to secure rest to the brain during that period. The use of stimulants is therefore contraindicated, especially strychnin. Inject morphin and raise the foot of the bed three feet so as to place the abdomen on a higher level than the head and thorax (chairs are better than blocks for this purpose), this position to be maintained until all symptoms of shock have worn off. Bandaging the abdomen tightly assists in raising the blood pressure. This bandage must not embarrass the movements of the chest; for the same reason heavy bedclothes must be supported on a cradle. Bandaging the extremities is also useful in some cases. "Increasing the total quantity of fluid in the circulation by infusion of normal saline tends to raise the blood pressure, and aids in recovery of vasomotor centers. Adrenin in suitable quantities added to the ^ Latham and Crisp English : "A System of Treatment, ' ' 93. 404 ANESTHESIA saline materially assists. Adrenin, they hold, acts directly upon the peripheral arteries, and causes a great increase in the blood pressure without acting upon the nerve centers. Its action is transitory, and it must be put directly into the vein. It should only be added to solutions which are introduced directly into the veins. It is useless to add to solutions which are introduced per rectum or subcutaneously. Eectal infusion is useful in cases of slight or early shock (or to prevent shock), as is also subcutaneous infusion." Intravenous Infusion in Serious Cases of Shock. — Infusion, to be effective, must be carried out continuously until the patient is well on the way to recovery and is out of danger. Transfusion of human blood is far more effective than any form of saline infusion. Pituitary Extract. — This is similar in action to adrenin, although as used at present the drug is not so powerful. It has the advantage over adrenin that its effects last from a half hour to one hour. It must also be injected into a vein. It can be administered in fairly large doses with safety, but subsequent doses have less effect than the original dose. Keen ^ recommends the following measures : " ( 1 ) The prevention of further shock; (2) the support of the circulation; (3) the securing of physiologic rest." Support of the Circulation. — Head-down posture increases blood in brain, heart, and lungs. Extremities and abdomen may be bandaged. Use heavy layers of cotton and broad flannel bandages. Crile's pneu- matic rubber suit is the best, as the pressure is under control, and the air placed in the suit may be warmed and the pressure increased or diminished without disturbing the patient. The blood pressure may be raised in this way frorii 15 to 40 mm. mercury. Saline infusions may be given. Physiologic rest is the most important consideration in the treatment of shock. "When the motor activity takes the form of obvious work per- formed, such as running, the depletion of the vital force, expressed by various phenomena, is termed physical exhaustion. When the expendi- ture of the vital force is due to stimuli which lead to no obvious work performed, especially if the stimuli are strong and the expenditure of energy rapid, it is designated as shoclc." Under nitrous oxid anesthesia the physiologic changes and the brain cell changes, following an equal trauma, were approximately one-third those following ether. Traumatized animals whose blood pressures were maintained by di- rect transfusion of blood, thereby eliminating the factor of anemia, still showed physical changes in their brain cells; animals similarly anes- ^Loc. cit. TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 405 thetized and transfused, but not traumatized, showed no change. "Shock is an overstimulation of the whole motor mechanism." Anoci-association. — "If the patient be kept free from any emotional excitations by special management and by narcotics, or be not permit- ted to know that the operation is to be performed at a special time, and if such patient be anesthetized in such a manner that no adap- Degreejs, 98 99 100 101 \01 103 Ethsr. < NaO. 1^ W H Anoci. Be&X?. 70 80 90 100 110 120 Ether. NaO. Ph Anoci. Fig. 148. — Chile's Abdominal Hystehectomy Chart. Temperature: each heavy line represents the average 5:00 P. M. temperature of ten patients during the first four days after operation. Pulse: each heavy line represents the average 5:00 P. M. pulse rate of ten patients during the first four days after operation. tive response is excited by such an anesthetic as the pleasant nitrous oxid, and if the field of operation be so completely blocked by local anes- thesia that no traumatic impulse reaches, the brain, and if in closing the wound another local anesthetic is employed that will block nerve imi- pulses for, say, twenty-four hours, thus preventing the after-pains, such a patient will then have been operated upon in such a manner that the motor mechanism has received no adequate stimulus." Hence there is no surgical shock, nor interference with digestion, nor nervous impairment afterward, i. e., no change in the circulation, the respiration, the digestive functions, nor the mentality of the patient. "Although ether anesthesia produces unconsciousness it apparently protects none of the brain cells against exhaustion from the trauma of surgical operations." Under nitrous oxid anesthesia there is approximately only one- fourth as much exhaustion, after equal trauma, as under ether. "Either nitrous oxid protects or ether predisposes to exhaustion under trauma." Causes and Prevention of Post-operative Gas Pains. — "The patient is anesthetized as usual, but the entire line of incisions is care- 406 ANESTHESIA fully blocked with novocain, including the peritoneum. If then, at the end of the operation and before the peritoneum is closed, there is applied Degree3 98 99 100 \0\ 102 103 Et^er. H W NzO. W H Anoci. Beaut>s. 70 80 90 100 no 120 Ether. Na.0. Anoci. Fig. 149. — Chile's Thyroidectomy Chart. Temperature: each heavy line represei.ts the average 5:00 P. M. temperature of ten patients during the first four days after operation. Pulse: each heavy line represents the average 5:00 P. M. pulse rate of ten patients during the first four days after operation. around the entire line of stitches a complete anesthetic block that will last a number of days (as 50 per cent alcohol or quinin and urea hydro- chlorid), and if in stitching the peritoneum every stitch is placed within this blocked zone, then the afferent impulses caused by stitch irritation are blocked, and hence cannot excite the protective mechanism of intes- death rate. % / 2 3 ^ 5 6 T p^r -ooo 1908 Cast loooCtS s Fig. 150. — Crile's Chart of Mortality Rate per Thousand of Operative Cases FROM Lakeside Hospital. The last thousand were under anoci. final inhibition. It has been found that such blocking does minimize or even prevent post-operative gas pains in all sorts of abdominal opera- tions.'^ Vasomotor Hyperactivity (Acapnia) — Henderson. — The chief opponent of the vasomotor paralysis or deoxygenation theory of shock is Yandell Henderson, the originator of the theory that shock is due to the hyperactivity of the vasomotor centers, as a consequence of the loss, TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 407 for some reason, of carbon dioxid, and the effort on the part of the organ- ism to compensate for this loss. We cannot, perhaps, better explain Henderson's theory than by quot- ing from one of his papers ^ an illustrative case : "A man in the prime of life was setting off fireworks when a giant A. B. C. D. Fig. 151. — Operations Under Anoci-association. A. Appendectomy. B. Herniot- omy. C. Hysterectomy. D. Cholecystotomy. (Crile.) firecracker exploded in his hand and shattered it. There was no con- siderable loss of blood. For two hours he suffered intensely, although he received a quarter of a grain of morphin. Then anesthesia with ether was attempted, and his breathing immediately began to fail. The anesthetic was withdrawn, and respiration improved. Three hours after the accident he stopped breathing quite suddenly. Artificial respiration and stimulants were ineffective, and he died. Yet his pulse was fairly A. B. C. Fig. 152. — Technique of Abdominal Operation Under Anoci-association. A. Infil- tration of skin and subcutaneous tissue with 1-400 novocain. B. Infiltration of fascia and muscle. C. Infiltration of posterior sheath and peritoneum. D. Peritoneum inverted; infiltration with H per cent, of quinin and urea hydrochlorid. (Crile.) good before and even for some minutes after respiration ceased. Why did that man die? In order to make the further discussion of my topic clear, I will present immediately the explanation to which, as it seems to me, all the data point. During the period after the accident his breathing was of the type which insupportable pain always excites. This hyperpnea involved a far greater ventilation of the lungs than normal breathing affords. Consequently the CO2 content of the blood, and finally also of the body as a whole, was greatly diminished. When the ^Henderson, Tandell: "Fatal Apnea and the Shock Problem," Johns Hop- kins Eosp. Bull, Aug., 1910, SI, No. 233. 408 ANESTHESIA anesthesia was attempted it was almost inevitable that respiration should show signs of failure. CO2 is the normal stimulant of respiration; there- fore, after this normal chemical stimulant to breathing had been re- duced, pain alone maintained the breathing. Anesthesia removed the pain. Finally breathing stopped for the very simple reason that there was not enough CO, left in the blood to excite the respiratory center to activity. To this condition of diminished CO2 content in the blood Mosso has given the name "acapnia," from the Greek "kapnos," smoke. Literally, acapnia means smokelessness. Perhaps I should remind you that the arterial l)lood normally contains 20 volumes per cent of oxygen, and 40 of CO,, and that the body as a whole has an enormously greater store of CO2 than of oxygen." Henderson instituted a long series of experiments Avhich are now too well known to need repetition here. His observations led him to the conclusion that the condition of low arterial pressure, noted in shock, is not due to fatigue or inhibition or failure of any sort in the vaso- motor center. On the contrary, in his opinion, this center does its full duty almost to the last. The failure of circulation appears, in his ex- perience, to be due to diminution in the volume of the blood by transu- dation of its fluids out of the vessels into the tissues, a process resem- bling edema. "It is a complex peripheral process," he says, "induced initially by the influence of acapnia upon the veins and capillaries and upon the tissues. Thus when death (or shock) follows intense physical suffering, not complicated by hemorrhage, there are two principal stages. At first the excessive breathing diminishes the CO, content of the blood. If, at any time after this condition of acapnia has been induced, the pain is greatly diminished, and the respiratory center is thus allowed to re- lapse into standstill, fatal apnea vera may occur. If, on the other hand, the pain is sufficiently continuous to keep the respiratory center con- tinually excited, then apnea is prevented, and the condition of acapnia becomes more and more acute and general until the circulation fails, and the subject sinks into surgical shock." Both fatal apnea and the more slowly developing failure of circulation, he holds, are due ini- tially to acapnia induced by the excessive breathing occurring under torture. He does not agree to the importance of the role ascribed by others to oxygen in maintenance of the function of the respiratory center. On the contrary, he considers that Mischer expressed the essential truth regard- ing the regulation of normal breathing : "Over the oxygen supply of the blood CO, spreads its protecting wings." Henderson considers that death from respiratory failure is explained as due to these "protecting wings." "Those cases of fatal apnea," according to Henderson, "which more than any other interest the clinician, are, I suppose, the failures of TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 409 respiration under anesthesia. If the patient ceases to breathe in his bed, it is his own fault, but if he does so on the operating table the anesthetist has to bear the responsibility. For such cases of apnea the acapnia hypothesis affords a simple explnnation. Anesthesia di- minishes the strength of inflowing afferent irritations. Furthermore profound anesthesia raises the threshold of the respiratory center for CO2. In other words, the respiratory center of a man or animal in pro- found anesthesia automatically maintains more than the normal COo content in the blood. Thus, when a man or a woman or a child has suf- fered prolonged pain, and thereby has been brought into a condition of more or less acapnia, the production of anesthesia by removing the affer- ent pain stimuli, and also by raising the threshold, that is, by dimin- ishing the sensitiveness, of the respiratory center for CO,, inevitably leads to apnea." Prevention of Acapnia. — The prevention of acapnia calls for the prevention of excessive pulmonary ventilation. According to Hender- son, the administration of morphin and full anesthesia diminishes the activity of respiration under pain, and thus prevents acapnia. If, how- ever, morphin and chloroform be administered to an animal which has suffered pain for some time, apnea is hastened unless carbon dioxid is also administered. In moderate degrees of shock, induced by irritation of afferent nerves or by exposure of the viscera, Henderson has found it possible to induce rapid recovery by the infusion into a vein of normal saline or Einger's solution saturated with carbon dioxid, and then making the sub- ject breathe an atmosphere of oxygen and carbon dioxid or oxygen alone. In profound shock he has found that these measures fail to effect an ultimate recovery. Treatment. — Henderson outlines two methods of treating acapneal respiration under anesthesia. One method involves the intratracheal insufflation of a gentle stream of oxygen gas, according to the method devised by Volhard. For man the quantity of oxygen should be not less than 400 c. c. per minute. The other method of restoration of breathing to which Henderson refers has been found by him to be remarkably successful in restoring dogs during apnea. It consists in the administration of air or oxygen containing 5 or 6 per cent of carbon dioxid, the breathing being started by one or two artificial respirations. As soon as the normal tension of carbon dioxid in the lungs is restored, spontaneous breathing imme- diately recommences and continues as long as the inspired air contains a sufficient quantity of carbon dioxid to stimulate the respiratory center. McKeson for the past five years has used an apparatus for measuring the blood pressure in connection with all anesthetics, for the special pur- pose of anticipating shock. His remarks follow : 410 ANESTHESIA THE INTERPRETATION OF PULSE, RESPIRATION, AND BLOOD PRESSURES WITH SPECIAL REFERENCE TO SURGICAL SHOCK "What is the purpose of taking blood pressures during opera- tions ? " 'Feeling the pulse' has proved to be an unreliable method in de- termining the pressure values of the pulse. And, if the anesthetist is to be acquainted with the condition of his patient, he must be able to determine quite accurately these pressures for comparison as the opera- tion proceeds. To anticipate shock and to apply remedial measures be- fore the process has become well advanced requires an earlier recogni- tion than is possible without the sphygmomanometer. "Before shock (excluding shock from hemorrhage) becomes so well established that it may be positively diagnosed clinically, the patient passes through certain circulatory disturbances which are indicative of the condition to follow as certainly as certain weather conditions fore- cast rain. "What are the important factors in making this interpretation ? "Let us first state briefly a few facts concerning the physiology in- volved in the maintenance of blood pressure. The heart is the pump; the great arteries are more or less elastic and admit more blood from the heart by distention; the arterioles are the 'shut-off' valves control- ling peripheral resistance and determining the volume of blood to pass through a certain group of capillaries; the capillaries and veins act in this connection as return tubes to the heart and lungs, which return the blood through the pressure of various muscles, gravity, and suction by the heart and lungs. "The pressure in the arteries before systole represents the conditions of resistance and elasticity of the vessels. Other things being equal, an increase in the diastolic pressure means more resistance; a decrease, less resistance in the arterioles. At the next ventricular contraction the heart must produce enough pressure to equal the diastolic pressure before the valves will open; from this point the remaining portion of the contrac- tion will produce the discharge of blood into the aorta, and is called pulse pressure — the discharge power of the heart. "The pulse pressure is the working pressure in moving the blood, and concerns the heart only. So that it represents the most important single guide to the power of the heart. "The systolic pressure represents the pressure developed during sys- tole, and is the sum of the diastolic and pulse pressures. It is evident that the systolic pressure will be more variable than the diastolic, for it must accommodate itself to variations in the heart rate and pulse pres- TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 411 sures, and is therefore not as valuable a sign as was formerly supposed in determining oncoming shock. "The heart must maintain a certain pressure in the aorta that its own tissues may be properly bathed in blood through the coronaries. This may be accomplished in falling pressures by increasing the output of the heart and, to some extent, by increased peripheral resistance, althoiigh, clinically, after arterioles once dilate, the heart must usually compensate by increasing its output, as they seldom regain their tone during operation. "Eespiration aids the heart in producing blood pressure in tin; lui- FiG. 153. — Blood Pressurs Apparatus as Used by McKeson. man subject. Intrapulmonary pressure is increased during exhalation, aiding the heart to force the blood out of the chest. This force under anesthesia normally increases the blood pressure from 5 to 10 mm. of mercury above the reading obtained during inhalation. During inhala- tion the blood is drawn out of the great veins leading into the thorax, so readily seen during extensive neck or breast operations; at the same time the capillary resistance in the lungs is greatly reduced, so the right heart can more easily force a large volume of blood over to the left side. And when exhalation begins again the lungs squeeze out the excess blood into the left heart, increase intrapiilmonary pressure, and again blood pressure is elevated. "It should be remembered that with the abdomen open the diaphragm cannot increase intra-abdominal pressure, and the return of blood from the abdomen at the time of chest aspiration (inhalation) will not be as perfect as usual, which may be an important element in venous stasis here. 412 ANESTHESIA "A respiratory rate of more than 30 per minute is too rapid to assist in moving the blood, throv/ing the whole burden on the heart. Also, a constant intrapulmonary pressure interferes with venous supply to the heart. "An obstructed airway of any considerable degree, on the other hand, increases the respiratory variation of blood pressure, but if the respira- tions are too long and powerful it has the same effect as a continued positive pressure — interfering with the venous return and increasing the danger of a dilated right heart. REMARKS OXYGEN BEBRCATHINO Percent NITROUS OXIDE RESP. PULSE AND D ^ liS ui -J lO " LOOO PRESSURE 5 O sssassss O O o . BEGAN ANESTHEIJC -, u • I ^ 500 r C ■ Abdominal manip 5 Traction on 500 - mesenten/ w •. > g 500 J^ ( Avvendectomy ' • V m S 500 • s Clostnrf wound ^ 500 • ■ 1 _ -] 1- ^ H _ <. _ - _ _ ^ _ _ -h _ J _ _ _ _ / _ _i _ _ _ _ _ _ - ^ S - - - - --^ -J - - - - - - - - - - - - present condition • ■ X f^ S z A Jl p j; _ J -1 s Fig. 154. — McKesoh's Blood Pressure Chart No. 3908. "In order to clarify our previous statements and to apply them to a concrete case, let us examine a copy of our chart ISTo. 3908; a woman aged 64, weight 120, in good physical condition, was operated on for ob- struction of the colon with adhesions, and the appendix was removed. An H. M. C. tablet containing 1/6 grain morphin was given hypodermi- cally about 1 hour before. The anesthetic was ^,0 and 0^ without novo- cain infiltration in the line of the incision. Just before anesthetization, the (S) systolic pressure was 135, the (D) diastolic pressure 90, making a pulse pressure of 45, pulse 82, respiration 20. "During the first 15 minutes of the anesthesia nothing happened ex- cept a very slight increase in respiration frequency. During the latter portion of this time abdominal manipulations and traction on the intes- tines was followed by a slight fall at (A) in the pulse rate, a 25 mm. fall of systolic, and a 10 mm. fall of the diastolic pressures. In the be- ginning we had a pulse pressure of 45 mm., which was probably nearly normal for this patient, while at the end of 25 minutes it was 35 mm. What had happened? "When the intestines were exposed, handled, and dragged up, and rough gauze pads introduced into the belly to paclc certain loops away TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 413 from the desired field, the arterioles relaxed and the diastolic pressure fell. With an easier outlet for the blood and a comparatively slow pulse, the pulse pressure weakened slightly and the systolic fell markedly. "This is not shock, but if it should continue as started it would re- sult in shock in about 30 minutes or when the pulse pressure is but 10 to 15 mm. and the diastolic is 70 mm. or less. There was no reason for apprehension in this case, for, between (B) and (C), when less trauma was inflicted while doing the appendectomy, there was a compensatory increase of the heart rate, bringing the pressures to their former posi- tions. Of course, this cost the heart 25 beats more each minute, but the reserve power in a heart not already complicated with disease is usually sufficient to keep up a rapid rate for several hours, provided that pres- sure is maintained. It shows here that the arterioles are still open, and even in the last 10 minutes, when more is used in the mixture, as the pulse falls the diastolic falls; but 10 minutes after the anesthesia and operation are completed the pulse, respiration, and blood pressure re- lations are practically reestablished as before the anesthesia was begun. "So it is possible by an intelligent interpretation of the pulse, respira- tion, and blood pressure to anticipate the occurrence of surgical shock at least 20 minutes and usually much longer. "Anesthetic overdosage, however, must not be confused with surgical shock, although many of the signs are similar in the relative overdosage cases, and the respiration and heart may be brought to a standstill in a very few minutes." Post-Anesthetic Toxemia The second of the major difficulties which may arise as a conse- quence of the administration of an inhalation anesthetic is post-anes- thetic toxemia. Acetonuria, acetonemia, acidosis, acid intoxication are terms applied to delayed chloroform poisoning, concerning which a voluminous literature has been compiled within recent years. Ether also is now believed to give rise to acid intoxication. It is the opinion of some observers, the senior author among this number, that so-called post-anesthetic toxemia exists only in cases in which there is already a tendency to acidosis, or in which this condi- tion is precipitated by careless technique on the part of the anesthetist. In every case the presence of acetonuria or other acid conditions should be ascertained beforehand, and treatment instituted to correct the trouble as nearly as is possible before the anesthetic is administered. Elimination, by bowels, kidneys, and skin, should be stimulated for sev- eral days previous to the anesthesia, and the tendency to hyperacidity should be counteracted by the administration of suitable alkaline medica- tion. An important part of this preparation is careful, attention to the diet. 414 ANESTHESIA Four or five days before the operation tlie patient should be given sodium bicarbonate, fifteen grains daily, until the urine is alkaline in reaction. Meats should be restricted or excluded, and the patient placed upon a strictly vegetable diet for this length of time. Two hours before the operation a saline enema, one pint or more, with one ounce of olive oil and one ounce of glucose, should be given. One hour before the operation small amounts of morphin should be administered, according to the patient's condition. (See Preliminary Medication, p. 70.) If chloroform is used at all, it should be used only in the beginning of the anesthesia, and a change should be made to ether at the second stage. The rule of Mortimer ^ in connection with these cases is a good one : "Never give chloroform alone except for rare and special reasons." Small amounts of chloroform may be used 'until the second stage is reached ; this excludes the element of fear, and is a desirable procedure if the psychic element is very much in evidence. This method is preferable to inducing the anesthetic with ether, which might give rise to very great fright and necessitate holding the patient. Beven and Favill ^ collected over twenty-nine scattered cases, seem- ingly identical, in regard to acid intoxication and late poisoning effects from chloroform and ether anesthetics. The first case reported is so typical of the poisonous after-effects of chloroform that all the facts in connection with it are worthy of being recorded. An unusually long time and a large amount of the anesthetic were required to establish surgical narcosis. The time of narcosis and opera- tion is not stated, but the patient was thoroughly conscious a short while afterward with a pulse of 102 and a temperature of 101°. About two days later the first symptoms of poisoning were marked, the mother of the child noticing that she was not quite natural in her remarks. The physicians were called, and found the child talking incoherently and exhibiting evidences of great fright. This mental condition appeared without warning, as all symptoms had pointed to an uneventful recov- ery up to this time (44 hours after the operation). There was a rising pulse, with unremitting delirium and a curious shrieking outcry. The delirium was partly controlled by small amounts of morphin. At regu- lar intervals a period of excitement — practically a convulsion — would occur, lasting for one minute or perhaps longer. Death occurred 110 hours after the operation, with a gradually rising temperature, irregu- lar and rapid pulse. Cheyne-Stokes respiration was present. During the last two days before the child's death a sweetish, acetone odor was noted on her breath. Other Cases. — Several clinicians have noted symptoms appearing from two to six days after chloroform narcosis. Violent and persistent ^Mortimer: "Anesthesia and Analgesia," 65. ^ Bevan, Artliur D., and Favill, Henry B. : J. Am. Med. Assn., Sept. 2, 1905. TREATMENT BEFORE, DURING, AND AFTER ANESTHESIA 415 vomiting, icterus, sometimes piercing shrieks, profuse sweating, and a picture of terror on the face seemed to be the clinical symptoms, also air hunger, as evidenced by deep breathing and cyanosis. Fatty changes have been noted in liver, heart, or kidneys, or all of these organs, on autopsy; acute yellow atrophy, fatty denegeration, or fatty infiltration of the liver have also been noted. Death usually occurs from exhaus- tion, the patient sinking into a state of coma from the third to fifth day. The urine contains albumin in all cases, and is usually scanty. Probyn- Williams ^ states that, while deaths have followed the inhalation of chloroform more frequently than any other anesthetic, cases have been reported with both ether and ethyl chlorid. Brewer ^ reports a case fol- lowing an operation for acute appendicitis. When death occurs from acidosis,"' it seems to be due to lack of oxy- gen, as there is struggling for breath and cyanosis. The symptoms are vomiting, sweetish odor of breath, face flushed, lips dry, weak, rapid pulse, restlessness, unconsciousness. In children the acetone is given off through the lungs. In adults it is excreted by the kidneys. Pathol- ogy of acidosis is fatty degeneration of liver, kidneys, and muscles. Con- ditions Tinder which acidosis may occur : Diabetes, carcinoma, digestive disturbances, starvation, gastric ulcer, excessive fat ingestion, infec- tious fevers, chronic morphinism, fatty liver, starvation (lack of carbo- hydrates), and following ether or chloroform anesthesia, in 120 cases etherized by the "cone method," acetonemia developed in 88.5 per cent. Of the same number with the drop method only 26 per cent showed acetonuria. ^ Probyn-Williams : "A Practical Guide to the Administration of Anesthet- ics," 166. ^Brewer: Ann. of Surg. (1902), 36, 481. ^ Hamblen : Univ. of Fenn. Med. Bull., .June, 1909. CHAPTER X ANESTHESIA BY INTEATEACHEAL INSUFFLATION Charles A. Elsberg, M.D. Definition. History. The Apparatus for Intratracheal Anesthesia in the Human Being : Apparatus ISTo. I ; Apparatus No. II ; The Catheter or Tube to Be Used ; The Introduction of the Tube. The Course of the Anesthesia. Errors Which May Occur in Technique: Accidents and How They May Be Avoided. The Indications for Intratracheal Anesthesia. The Value of Insufflation of Pure Air or Air and Oxygen AS A Method of Artificial Eespiration. Bibliography. Definition. — Intratracheal insufflation is the name given by Meltzer and Auer to a method by means of which a mixture of air and ether is driven deep into the trachea by means of external pressure through a tube which has been introduced into the trachea through the larynx. History. — Physiological Basis. — Animal Experiments. — In 1909 Meltzer and Auer ^ first published an account of their experiments, which culminated in the method of anesthesia to which they gave the name "intratracheal insufflation.'^ Physiologists had long known that animals could be kept alive by blowing air into the lungs, but this method had never been satisfactorily applied to the human being. Fell, O'Dwyer, Kuhn, Volhard, and others attempted to apply methods of this kind to man. Hirsh, Robinson, and others showed that the blood could be well oxygenated by passing a stream of oxygen intermittently through a tube to the bifurcation of the trachea. It is well known that breathing is kept up by alternating respiratory movements and that the proper ventilation of the lungs depends upon the normal activity of the muscles of respiration and the intact condi- tion of the walls of the thorax. Meltzer and Auer discovered that the proper exchange of the air in the lungs can be accomplished by an ^Meltzer and Auer: J. Eocper. Med., 1909, 11, 622. 416 ANESTHESIA BY INTRATRACHEAL INSUFFLATION 417 almost continuous stream of air passing in one direction. They found that if they passed a tube through the larynx of a dog almost to the bifurcation, and blew air through this tube in a continuous stream, the animal could be kept alive for many hours, even after all voluntary respiratory movement had been abolished by curare. By allowing the stream of air to pass over the surface of ether in a bottle, they found that animals could be very satisfactorily anesthetized. In these animals it was possible to open both pleural cavities widely and to have the animals remain alive for many hours. The apparatus used by Meltzer and Auer ^ was a very simple one. Fig. 155. — Meltzer's Simple Apparatus for Intratracheal Insttfflation. B, foot- bellows; S. T, stopcocks; E, ether bottle with S. C, stopcock and F, funnel; M, manometer; S. V, mercury safety valve; IN-T, intratracheal tube. It consisted of a foot bellows connected by tubes with a bottle containing ether and with a mercury manometer. The tubes were so arranged that more or less of the air from the bellows passed over the surface of the ether, and thus became more or less saturated with ether vapor. The air and ether mixture was blown in at a pressure of 15 to 20 mm. of mercury. The only condition essential to success was that the tube be of a size less than one-half of the diameter of the trachea, so that the air and ether which passed up the trachea and out through the larynx and mouth in a continuous stream had free escape. Later it was found of advantage to interrupt the stream three to six times a minute, so as to allow the lungs to partially collapse for a moment at times, and thus to get rid of small quantities of carbon dioxid which are apt to remain in the pulmonary alveoli. With this simple apparatus, Meltzer and Auer ^ made many investi- ^ Meltzer and Auer: J. Exper. Med., 1909, 11, 622. ^Med. Bee, 1910, 77, 487. 418 ANESTHESIA gations upon animals, and they recommended the method as an emi- nently safe one for anesthesia. They pointed out that it might have great value for intrathoracic operations, and that it was an ideal method for artificial respiration. Elsberg ^ made a large number of experiments on animals, and performed numerous operations upon the lungs of dogs, and Carrel ^ used the method with great satisfaction in his operative work upon the heart and thoracic blood vessels of dogs. In all of these experiments one or both pleural cavities were widely opened, the heart action remained good and regular, superficial respiratory movements per- sisted. In other words, the method of intratracheal insufflation was effec- tive in preventing collapse of the lungs when the thorax was opened. Later, Nordman,^ Schlesinger,* Boothby and Ehrenfried,^ Fischer,® and others investigated upon animals the value and advantages of the method from the standpoint of the anesthesia and with regard to its efficiency in the presence of a single or double pneumothorax. The reports of all these authors have been uniformly in favor of the method. From an extensive and thorough experimental investigation of anes- thesia by intratracheal insufflation of air and ether, Meltzer '' concludes as follows: "The essentials of the method of intratracheal insufflation consist^ in the introduction deep into the trachea of a flexible elastic tube, the diameter of which has to be much smaller than the lumen of the trachea, and ^ the driving through this tube of a nearly continuous stream of air which returns through the space between the tube and the walls of the trachea. The distinguishing features of this method consist in the following two new principles: 1. By bringing the pure air di- rectly to the larger bronchi, and by driving out the vitiated air from these bronchi through the force of the returning air stream, that part of the "^death space' is eliminated which is represented by the mouth, pharynx, larynx, and trachea. The chief aim of the complicated nervous and muscular mechanisms of respiration is to establish an efficient venti- lation, capable of overcoming the obstacles offered by the mentioned 'death space.' A well-arranged intratracheal insufflation is fully capable of relieving and replacing the normal respiratory mechanism. 2. The practically continuous recurrent air stream prevents the invasion of in- different or infectious foreign matter from the pharynx into the trachea. 'Elsberg: Med. Bee, 1910, 77, 493. '^ Carrel: Med. Bee, 1910, 77, 491; J. Am. Med. Assn., 1910, 54, 28. ='Nordman: ArcMv f. Tclin. CUr., 1910, 92. * Schlesinger : Archiv f. Tclin. Chir., 1911, 95. 'Ehrenfried: Boston Med. and Surg. J., 164, 532 ^Eischer: Surg. Gyn. and Ohstet., 1911, 13, 566. 'Meltzer: J. Am. Med. Assn., Aug. 12, 1911. « Meltzer and Auer: J. Exper. Med., 1909, 11, 622. ^Meltzer: J. Am. Med. Assn., Aug. 12, 1911. ANESTHESIA BY INTRATRACHEAL INSUFFLATION 419 "The usefulness of the method is at least threefold. 1. It is capable of keeping up an efficient respiration in cases in which the normal mech- anism of external respiration fails. 3. It overcomes efficiently and con- veniently the difficulties pre- sented by double pneumothorax. 3. It offers a safe and reliable method for anesthesia, especial- ly for the administration of ether." Meltzer and Auer and the investigators who took up their work thus demonstrated that in animals the method of intra- tracheal insufflation is very effi- cient both for anesthesia- in gen- eral and for thoracic operations in particular. Its first applica- tions in the human being were made by Elsberg/ who was soon followed by other surgeons in the United States and else- where. The Apparatus for Intra- tracheal Anesthesia in the Hu- man Being. — A very simple ap- paratus constructed upon the plan of the one used in the lab- oratory can easily be put to- gether by anyone. Such an ap- paratus would suffice in an emergency. The construction and working of the one sug- gested by Meltzer can be easily understood from the diagram (see Fig. 155). For general use in the human being, a more complete apparatus is necessary, one that cannot get out of order, and which is surrounded by every possible safeguard in case of trouble with any of its parts. The essentials for such an apparatus are: (1) A source of air (elec- tric blower, foot bellows, hand pump) ; (2) a system of tubes connected with an ether reservoir and a mercury manometer; (3) a regulator or automatic blow-off that should prevent too great pressure in the tubes; ^Elsberg: Am. Surg., Feb., 1911; June, 1911; Dec, 1911. Fig. 150.- -Elsberg's Appaeatus, for Hos- pital Use. 420 ANESTHESIA (4) a warm water tank, by means of which the air stream can be warmed and moistened. For hospital use, it is advisable to have an apparatus which works automatically, and to reserve the foot bellows as an addition which can be used if the motor and blower are out of order, or if there is no elec- tric current. Elsberg devised two forms of apparatus, viz.: (1) an ap- paratus meant for hospital use; (2) a smaller and more easily portable ap- paratus. A description of these fol- lows. Apparatus No. 1 (see Figs. 156 and 157). — The entire apparatus is contained in a wooden box 38^/^ inches long, 11 inches deep, and 18 inches wide. It is easily transport- able. The box is placed on the floor near the head end of the operating table, and the front is turned down^ in order to expose the interior, which contains the following (Fig. 157). By means of the switch A and the rheostat B the electric current is carried to the 1/6 horsepower motor C, which drives the blower D. The air passes through the tube E and the oil filter F and the tube G into the bottle H. This bottle contains hot water, so that the air, as it bubbles through the water, is warmed, washed, and moistened. The current of air then passes through the tube I to the rubber tube, which is connected to the intratracheal catheter. To this tube. No. 1, is connected the ether reservoir J. The ether reservoir consists of a glass jar, which is held air-tight against its cover by a spring clamp below. The cover contains the open- ings of two tubes (X, X'), which are connected with the main tube I. The hand wheel K, which moves an indicator on a scale above it, is ar- ranged to control the air passing through the tube I. When the indi- cator stands at zero at the scale, pure air is passing through the tube I. As the indicator is turned, more and more of the air is diverted into the one tube (X), which leads into the ether reservoir. When full ether is turned on, all of the air has to pass into the ether reservoir and over the ^ The box is now arranged so that the front can be entirely removed. Fig. 157. — Diagram to Explain the Parts of Elsberg's Apparatus No. 1. The letters refer to the letters in the text. ANESTHESIA BY INTRATRACHEAL INSUFFLATION 421 surface of the ether, so that it becomes saturated with ether vapor. When the indicator shows that pure air is passing through the tube I, the tubes which lead into the ether reservoir are closed, and the ether reservoir can be removed if necessary and refilled. The manometer L is connected with the tube I, and records the pressure of the air current which is flowing through it. The ends of the Fig. 158. — Elsberg's Simplified Portable Apparatus for Intratracheal Insuffla- tion. To show the motor and blower. manometer tube have hard rubber stopcocks, which can be closed when the apparatus is to be transported — a possible spilling of the mercury in the manometer being thus prevented. The tube M leads into the main tube G and has also a stopcock, and to its tip the tube from an oxygen tank can be connected so that oxygen can be added to the air if desired. The tube P leads to a foot bellows, which has been added to the apparatus as a safety device if anything should happen to the motor or blower, or to be used where no electric current is available. When the stopcock N is closed and is opened, and the foot bellows used, the air passes into the tube G' and into the water bottle. When the stopcock IST is open and is closed, no air can 422 ANESTHESIA enter the main tube from the bellows, and air passes to the water bottle from the blower. It takes only a moment to turn the two stopcocks so that one can instantly switch from air from the blower to air from the foot bellows and vice versa. The water bottle H is held firmly in place by a clamp. The tubes from it are connected to the main tube by bayonet points, so that the Fig. 159. — Elsberg's Apparatus. Lower compartment closed. bottle can be easily removed when it is to be filled or emptied. The per- forated cork is held firmly and air-tight by a clamp. The apparatus and its handling are simple. When it is to be used, the water bottle is first one-third filled with hot water, the stopcocks on the manometer opened, the stopcock JST opened and closed, the switch turned on, the rheostat turned on full, and the motor and blower thus set in motion. The stopcock M is left wide open. As soon as the apparatus has been connected with the intratracheal tube the stopcock M is slowly turned until the manometer shows that the pressure of the air is 20 mm. The percentage of ether is regulated according to the depth of the anesthesia ; usually the indicator has to be turned until it shows that half or full ether is being used. By means of the stopcock at I (below the manometer), the air and ANESTHESIA BY INTRATRACHEAL INSUFFLATION 423 ether current can be diverted from the iiitralrachcal tube so that no air enters the intratracheal tube, but all of it escapes through the open stop- cock. The management of this apparatus is extremely easy. From the mo- ment the power is turned on and the pressure regidated, the anes- thetist's principal duties consist in watching the pressure gauge and occasionally interrupting the current of air so as to momentarily collapse the lungs. He can be seated near the table so as to observe the pulse of the patient. Apparatus No. 2. — This apparatus is much smaller than No. 1. It can be easily carried around like a handbag. It is 21 inches high, 20 inches broad, and 9^/2 inches wide (Figs. 158 and 159). The apparatus is similar to No. 1, but is much lighter and nnich more compact. The motor and blower are underneath in a closed compartment. At A the foot bellows, which lies in a compartment above, is to be attached. B is the stopcock for regulating the pressure, C is a simple lever by which the anesthetizer can switch from air from blower to air from bellows. The lube D leads into the metal water tank in the inside of the box. E is the ether reservoir held by the eccentric below. Above this is the ether regulator. F is the manometer, G the safety valve allowing regulation of pressure. H is the stopcock for making interruptions of the current.^ The apparatus of Janeway is very complete, but very complicated (Figs. 160A and B). The following description will serve to explain the various parts of the machine. No. 1 is a motor which turns the wing blower 2. From the blower the air passes through the air filter and muffler 3. By the valve 4 the current of air may be divided into two reciprocally varying quantities; one portion passes directly over the heated water (heated by electricity) in jar 5, while the other portion passes through jar 5, after first passing over the surface of ether in jar 6. Thus the whole current of air or any desired proportion may be mixed with ether, and in this manner varying quantities of ether supplied to the patient. Provision is also afforded for still further saturating the air with ether by valve 7, which is so arranged that a small quantity of the air passing through jar 6 may be made to bubble through only the top layers of the ether irrespective of the level of the ether in the jar. The blow-off valve 8 prevents any injurious excess of pressure, and valve 9, operated by worm wheel 10, mechanically interrupts the current of air passing to the patient at any desired intervals. In Fischer's apparatus (Fig. 161) the air pressure is obtained by means of a hand pump. Fischer published a complete description of his apparatus,^ but a study of Figure 161 will allow the reader to gain a fair idea of it. ^ A full description of this apparatus will be found in the Ann. Surg., 1912. ^ Surg. Gynec. and Obstet., Nov., 1911. Fig. 160a. Fig. 160b. Fig. 160a and b. — Janeway's Apparatus. ANESTHESIA BY INTRATRACHEAL INSUFFLATION 425 Ehrenfried's apparatus (Fig. 162) has the merits of simplicity, but, like Fischer's apparatus, has no safety device by means of which the method can be continued if any part of the main apparatus is broken or out of order. The Catheter or Tube to Be Used. — The tube which is to be in- troduced into the trachea must be fairly rigid, so that it cannot be coughed out of the trachea when it is once in place. A soft rubber tube should never be used. Not only is the introduction of a soft rubber tube more difficult, but it is not rigid enough, as it might be compressed if a spasm of the larynx should occur. The ordinary silk- woven urethral catheter with a side opening near its end fulfills all requirements. It has Fig. 161. — Fischer's Apparatus. The handle of the hand pump is not shown in the photograph. the additional advantage that it can be obtained everywhere. The cathe- ter should have two marks upon it — one 13 centimeters and a second 26 centimeters from the tip. The average length of the adult trachea is 12 to 13 centimeters ; of the thyroid cartilage, 5 centimeters ; of the distance from the incisor teeth to the glottis, 14 centimeters. Therefore, if the tip of the intratracheal tube is 26 to 27 centimeters from the incisor teeth, it will lie about 5 centimeters or less above the bifurcation of the trachea. The size of the catheter must, of course, vary with the diameter of the trachea and the size of the larynx. For the adult, it is advisable to use a tube of the size 24 of the French scale. The diameter of this size of tube corresponds to about one-half of the length of the glottis, as seen through the direct laryngoscope. Sometimes a somewhat larger cathe- ter must be used, but it is always better to use a tube that is too small than one that is too large. In children the catheter must be correspondingly smaller. The 426 ANESTHESIA length of the catheter in the trachea will vary with the size of the child, but it has been found that in general the length of the catheter that should be below the glottis measures about the same as the length of the tube from the glottis to the incisor teeth. In other words, if the ^0fUm ^^3_ 1^ Fig. 162. — Ehrenfried's Apparatus for Intratracheal Etherization. (Driven by foot pump which is not shown in the photograph.) It consists essentially of a copper hot-water jacket, holding a Wolffe bottle containing ether. There are cocks by which the air from the bellows may be sent in any proportion through a coil in the hot water, over the surface of the ether, or made to bubble through ether. Attached to the outside of the jacket is a mercury bottle safety-valve. On the delivery tube is a con- trivance to filter the air and to prevent droplets of condensed ether from being car- ried over into the lungs. catheter has been introduced as far as the glottis, it will have to be pushed again as far downward as to have the tip in the proper part of the trachea. The Introduction of the Tube. — In many patients it is possible to '^/^*:st^ Fig. 163. — Cotton-Boothby Introducing Cannula, Ehrenfried's Modification, FOR Soft-Rubber Tubes. introduce the catheter after the epiglottis has been pulled forward by means of the index finger, which acts also as a guide. In children the intubation is always easy by this means. In many adults the epiglottis ANESTHESIA BY INTRATRACHEAL INSUFFLATION 427 cannot be reached by the finger; in these patients the intubation is im- possible by touch alone, and a special instrument must be used. Vari- ous guides with a laryngeal curve and variously shaped laryngeal forceps have been tried. None of these has been uniformly satisfactory, but Boothby and Cotton recommend their introducer (see Fig. 103), and Ehrenfried has one of his own (Fig. 164). I have found that the tube can always be quickly and easily introduced when the larynx is in plain view, which can be easily accomplished by means of the Jackson direct laryngoscope (see Figs. 92 and 1G5). With a very little practice, one can learn to use this instrument and obtain an admirable view of the glottis, so that the catheter can be readily introduced between the vocal cords. Anyone who is to use the method of intratracheal anesthesia Fig. 164. — Ehrenfried's Introducing Forceps for Stiff or Soft-Rubber Tubes. should practice the method of the exposure of the larynx with the Jack- son instrument. If the larynx is well cocainized it is possible to introduce the cathe- ter and anesthetize the patient by means of intratracheal insufflation of the anesthetic. The introduction of the tube is unpleasant, however, and the beginning of the insufflation may cause the patient much discomfort because of the reflexes at the bifurcation of the trachea. In the cases where a preliminary anesthesia by inhalation is inadvisable (where there is danger of collapse of the trachea, etc.), the best plan to follow is to introduce the catheter after the larynx has been well cocainized; then to anesthetize the patient by means of ether given through a mask or cone held over the end of the catheter and the mouth. In general, it is best to give the patient a dose of morphin and atropin and then to anesthetize him in the usual manner Avith ether. When the patient is well under anesthesia, he is brought into the operat- ing room and placed upon the operating table, with the head hanging well downward over the end of the table and the mouth held open with an or- dinary mouth gag.^ The direct laryngoscope is then introduced and ^ Preliminary cocainization of the larynx is unnecessary. 428 ANESTHESIA pushed along the posterior wall of the pharynx until the epiglottis is in plain view. The epiglottis is pulled well forward by the beak of the instrument and the glottis well exposed. One usually obtains a fine view of the larynx, can clearly see the opening between the cords, and can ^^MWMjWi Fig. 165. — Jackson's Direct Laryngoscope. (See p. 226.) estimate its size and length. If there is any difficulty in exposing the vocal cords, the head and neck are pulled forward as a whole, the head being kept bent backward as before. A catheter whose outside diameter measures about one-half of the length of the glottis (in general No. Fig. 166. — Elsberg's Clip to Hold the Intratracheal Tube in Place. The rubber covered arms B B' lie between the teeth and hold the tube between them. The wires W W fit over the ears like the wires of spectacles. 24 F can be used) is then selected. This is introduced through the laryn- goscope and into and through the larynx. The tube is then pushed for- ward until the second mark on it shows that the tip is 3 to 5 centimeters above the bifurcation of the trachea. Air will now be heard rushing in and out through the catheter. The patient is very apt at this time to ANESTHESIA BY INTRATRACHEAL INSUFFLATION 429 have an attack of spasmodic coughing and to hold his breath. This need not cause concern, as respiration will soon begin again. One must be sure that the tube is in the trachea and not in the esophagus. If one is in doubt, the catheter must be withdrawn and reinserted. One soon learns, however, to recognize the sound of the air rushing in and out through the tube. The tube is now held in place and the laryngoscope withdrawn, the entire manipulations thus far having occupied only a minute or two. The patient is then pulled back upon the operating table. A small clip serves to hold the catheter in place (see Fig. 166). It consists of a clip bent at right angles, the branches covered by rubber tubing. This fits between the teeth so that the patient cannot bite the catheter, which is held firmly in place. The clip is held in position by elastic wires, which fit over the ears like a pair of spectacles. After the clip is in place the mouth gag is removed, the catheter is connected with the connecting tip of the tube which leads from the insufflation appa- ratus, and from which the mixture of air and ether is flowing, and the insufflation is begim. The Course of the Anesthesia. — Ether is the safest anesthetic to use for intratracheal insufflation. The dosage of chloroform has not yet been sufficiently well worked out. Nitrous oxid and air or oxygen can also be given by insufflation. The ether anesthesia is usually very sat- isfactory. The patients are quiet, their musculature is relaxed, they breathe quietly and superficially. Some respiratory movements should always persist, and the anesthetizer should never keep the pressure, as shown by the manometer, so high that active breathing ceases alto- gether. If the catheter that has been introduced into the trachea is of cor- rect size and in the proper position, the face of the anesthetized patient will be of a pink, rosy color, with the veins of the forehead slightly prom- inent. The pulse is full, bounding, and regular. If the patient is cya- nosed, it means that the tube is not deep enough in the trachea or that too large a tube has been used. When the insufflation is begun, the patient may have a short attack of spasmodic coughing. This need cause no concern, and the insuflla- tion can be continued. The cough will sometimes persist if the end of the intratracheal tube is too near the bifurcation; it must then be with- drawn one or two centimeters. There is a complete absence of mucus rattling in the throat during the entire period of the insufflation. It is advisable to insufflate pure air for a few minutes at the end of the anesthesia in order to blow out the anesthetic from the lungs and trachea. Then the patients will awaken very quickly; they will often answer questions before the dressings have been applied. When the in- 430 ANESTHESIA tratracheal tube is withdrawn, there is often a short period of apnea, then regular deep breathing again begins. Cough and expectoration do not occur after anesthesia by intra- tracheal . insufflation unless the patient had a pulmonary lesion before the operation,- or an operation was performed upon the lungs. No pul- monary complications, of even the mildest kind, have been observed in more than 500 anesthesias. As soon as the patients are awake, they speak freely, are not hoarse, and do not complain of pain or discomfort in the throat. The larynx and trachea have a remarkable tolerance for the tube, which can remain in place for hours without danger. Post-operative vomiting is certainly quite unusual after intratracheal insufflation. This is probably due to the fact that no ether vapor can be swallowed. The patients seem to be less apt to show symptoms of shock than those anesthetized for long operations by ether inhalation. They are never too deeply under the anesthetic; in no instance has dilatation of the pupils as an evidence of too deep an anesthesia been observed. Occasionally, with patients upon whom an abdominal operation is to be performed, complete relaxation of the abdominal muscles is not obtained. These patients will also be found to be refractory to ether anesthesia by inhalation. Errors Which May Occur in Technique. — When the technique of intratracheal insufflation is once learned and the apparatus used by the anesthetizer is understood, errors or accidents should never occur. Spe- cial attention must be paid to the following features of the method. The catheter that is used should be too small rather than too large, so that there is never an interference with the free escape of the air and ether by the side of the tube and out through the larynx and mouth. If the proper size of intratracheal tube is used, there should be no danger of the over distention of the lungs. The Elsberg apparatus is arranged so that no excess of pressure in the lungs can occur. Every apparatus should have an automatic safety valve or blow-off, to act as a safeguard against a temporary or prolonged over-pressure, which might be injuri- ous to the lung tissue. Accidents, and How They May Be Avoided. — The accidents that have occurred so far have been due to errors in technique. In the case of Fischer,^ one of the tubes which led into the ether reservoir was under the surface of the ether, and, by turning the wrong stopcock, pure ether was blown into the lungs. The tubes which lead into the ether bottle should never be below the surface of the ether; in fact it is only neces- sary that they reach into the cover of the ether reservoir. In three other cases, two of which resulted fatally, the pressure was too high, so that injury to the lung tissue and emphysema in the sub- ^Loc. cit. ANESTHESIA BY INTRATRACHEAL INSUFFLATION 431 cutaneous tissue resulted. This could not have occurred if tin; appa- ratus had been provided with a safety valve for the prevention of excess of pressure. In one of the cases an intratracheal soft rubber tube was pushed down until it completely filled one of the branches of a bronchus, allowing no air to escape. With a proi)er a|)])aratus and the proper technique, all these accidents could have been avoided. In Mt. Sinai Hospital almost 500 patients have been anesthetized without accident. Another advantage of the method of intubation, in which the vocal cords are brought into view, is that the catheter can be introduced when the glottis is open, no force being necessary in pushing it down into the trachea. It need hardly be mentioned that one must be sure that the tube is in the trachea and not in the esophagus, otherwise overdistention of the stomach could easily occur. It is probable, however, that in such a case the air would be regurgitated as fast as it entered the stomach. The anesthetizer should never give an anesthetic by insufflation un- less he thoroughly understands the working of the apparatus he is using, nor should he forget to interrupt the entering stream of air and ether 3 to 4 times a minute. To sum up particular points to which attention must be paid, the anesthetizer must be certain: (1) That the catheter is in the trachea; (2) that it is not too far down — too near to or beyond the bifurcation; (3) that there is a safety valve on his apparatus; (4) that the interrup- tions in the air stream are made; (5) that respiratory movements per- sist. The Indications for Intratracheal Anesthesia. — Anesthesia by intra- tracheal insufflation is of value : (1) In thoracic surgery (whenever the thoracic cavity has to be in- vaded, to prevent the collapse of the lungs). (2) In operations upon the head and neck, where the anesthetizer can be out of the way or where the giving of the anesthetic is ordinarily difficult, as in bilateral suboccipital craniotomy or laminectomy, where the patient has to lie flat on the abdomen. (3) It is almost indispensable in those operations in the mouth where the pharynx and larynx must be kept free of fluid or blood. The stream of air and ether which is continually escaping from the larynx and mouth blows out any blood that might run down the throat, so that the operator need have no fear of any passing into the trachea. In such operations as complete removal of the tongue, removal of the upper or lower jaw, excision of malignant disease of the tonsil, the intranasal or intrabuccal approach to the hypophysis, etc., packing the pharynx is unnecessary. These operations are made much easier when the patient is anesthetized by the intratracheal method. The tube is kept in one cor- 432 ANESTHESIA ner of the moutH, and is never in the way of the operator. In the opera- tion of laryngectomy, intratracheal anesthesia is advisable. (4) Operations around the trachea, especially removal of the thy- roid gland, can be made much easier when the patient is anesthetized by intratracheal insufflation. The interference with the smoothness of the anesthesia when the trachea is pressed or pulled upon is avoided, and there is no danger of collapse of the trachea. (5) In operations in which there is danger of vomiting and aspira- tion of vomited material. Thus in operations for intestinal obstruction done under intratracheal anesthesia, the danger of the patients "drown- ing'^ in their own vomitus is avoided. (6) In prolonged operations, and with cachectic individuals. Shock seems particularly rare in patients anesthetized by this method. The future may show that intratracheal anesthesia will have a still larger field of usefulness than that here outlined. The Value of Insufflation of Pure Air or Air and Oxygen as a Method of Artificial Respiration. — This is a feature upon which too little stress has thus far been laid. Whenever there is need for prolonged artificial respiration, such as in opium poisoning, drowning, etc., the method will surely be very useful. In several instances we have kept patients alive in good condition for three, four, six, or seven hours although during that time not a single respiratory movement was made. The color of the patient remained pink, and the blood was well aerated. It is a valuable characteristic of this method that the patients need not breathe in order to have oxygenation of the blood occur, the apparatus doing the breathing for them. In this respect the method differs from all others for this purpose. It may be added that it has the same advantage over both the positive and negative pressure methods for thoracic surgery. In the latter the respiratory movements of the patient are absolutely necessary, aeration of the blood being impossible without them. With intratracheal insufflation oxygenation of the blood will occur just as well whether or not the patient makes respiratory movements. BIBLIOGRAPHY Boothby and Cotton: Surg. Gynec. and Obstet., 1911, IS. Elsberg: Langenbech's Arcliiv, 1911. linger: Berl. Tclin. Wocli., 1910, 1748, Woolsey: N. Y. State J. Med., Apr., 1912, 12, No. 4, 167. CHAPTEE XI ANESTHESIA BY COLONIC ABSORPTION OF ETHER AND OIL- ETHER COLONIC ANESTHESIA PAET I ANESTHESIA BY COLONIC ABSORPTION OF ETHER Walter S. Sutton, A.B., A.M., M.D., F.A.C.S. History. The Physiology of Colonic Anesthesia. Development of the Method. Sutton's Apparatus : The Generator. The Afferent and Efferent Tube Systems. Technique of Method: Preparation of the Patient; The Admin- istration ; After-treatment. Discussion of Cases. Conclusions : Indications ; Contra-indications ; Advantages ; Dis- advantage. . History. — The high efficiency of the intestinal mucous membrane of vertebrates in general as a transmitter of gases to and from the blood stream has long been recognized. As early as 1808 Erman ^ opened the abdomen of cohitus fossilis, and observed that when air was swallowed the liver and the intestinal veins of the fish became bright red; while when hydrogen or nitrogen was substituted the color of the organs changed to dark purple. Baumert,^ in 1855, analyzed the gas passed per rectum by the same kind of fish, and found a marked decrease in the oxygen content and corresponding increase in nitrogen when swallowing of air had been prevented for several hours. Jobert,^ in 1877, discov- ered that in callichthys asper, a Brazilian fish, air-swallowing is essen- tial to life, the fish dying in about two hours if prevented from the exer- cise of this form of accessory respiration. In mammals, also, similar * Erman: Aim. d. Phys. und Chem., 1808, 30, 113. ^ Baumert : ' ' Chemisclie Untersuchungen u. d. Respiration d. Schlemmpoit- gers," Breslau, 1885, 24. » Jobert: Ann. d. Soc. Nat., 1877, 5, No. 8. 433 434 ANESTHESIA phenomena have long been known. Thu.s, Panl Bert/ in 1870 found that if the trachea of a kitten be clamped the animal will die of asphyxia in about 13 minutes, but, if the intestine be inflated with air, life may be prolonged for 21 minutes. A similar absorption of oxygen by the in- testinal circulation in man is indicated by the results of Tappeiner,^ who, in 1886, on analysis of gases from various portions of the alimentary canal of an executed criminal, found in the stomach 9.19 per cent of oxygen, in the ileum only a trace, and in the colon and rectum none at all, while the percentage of carbon dioxid showed a regular increase from stomach to colon. Recognizing this activity of the intestinal mticosa, the early experi- menters with ether as an anesthetic attempted its administration by this route. The method is first mentioned in Pirogoff's ^ work on etheriza- tion, published in 1847. The original idea of Pirogoff was the introduc- tion of liquid ether into the rectum. Being warned by Magendie that this could not be done with impunity, he devised the method of vaporiz- ing the ether by means of heat and administering the drug in this form. He reported 81 cases with two deaths, but unfortunately failed to give a detailed report of the latter. In the same year, Eoux,* y'Yhedo,^ and Duprey *' employed injections of liquid ether, pure or in aqueous mix- ture, with the result of producing complete anesthesia. Pirogoff, in par- ticular, wrote enthusiastically of the advantage of the rectal method, even expressing the belief that it might supplant the inhalation pro- cedure. The method, however, disappeared from current literature, not to reappear until 1884. In this year Molliere '^ revived interest in the subject, introducing a new technique, in which he employed a Richardson hand bellows for forcing the ether vapor into the intestine. This method he later abandoned in favor of the earlier process of placing the ether container in a water bath (for which he recommended a tem- perature of 120° F.) and employing the pressure incident to the genera- tion of vapor to force the latter into the gut. Before the close of the year 1884 Yversen, Hunter, Bull,® Weir,^ Wancher,^° and Post ^^ had recorded their experience with the method. iBert: Physiol, compt. de la respir., Paris, 1870, 173. 2Tappeiner: Arheiten a. d. path. Institut su Miinchen, 1886. 3 Pirogoff : ' ' Eecherches pratiques et physiologiques sur 1 'etherization, ' ' St. Petersburg, 1847. 4Roux: J. d. I'academie d. Sciences, 1847, 18. 5 Y 'Yhedo : Gazette med. d. Paris, 1847. 6 Duprey: Academic royale de medecine, March 16, 1847. 7 Molliere: Lyon medical, 45, 1884. 8 Bull: N. Y. Med. J., March 3, 1884. 9 Weir: Med. Rec, 1884. 10 Waneher : Cong, internat. d. sciences med., 1884. 11 Post : Boston Med. and Surg. J., 1884. ANESTHESIA BY COLONIC ABSORPTION OF ETHER 435 Among these cases a number showed more or less marked diarrhea and melena and one death was directly traceable to the procedure. The method again fell into disuse, not to be revived until 1903, when Cunningham added to the technique of administration a new feature in the employment of air as a vehicle for carrying the ether vapor into the intestine. The first publication of Cunningham (written jointly with Leahy ^) appeared in 1905, being preceded by articles by Dumont,^ and Krugeline,^ the latter reporting 43 cases without untoward symp- toms. Stimulated by the records of improved results following the use of the Cunningham technique, many surgeons and anesthetists hastened to give the method a new trial, with the result that the subject has now acquired a considerable literature. In 1906 Stucky * reported 4 cases with favorable comment on the utility of the method. In the same year, Lumbard ^ reported four lapa- rotomies done under this method of anesthesia. Buxton,^ in the 1907 edition of his "Angesthetics," in speaking of '^rectal etherization," says : "I have now used the method pretty exten- sively, and find it to answer admirably for operations about the mouth, nose, and post-buccal cavities, for intra- and extralaryngeal operations, for staphylorrhaphy, and for operations for the relief of empyema. For the removal of the tongue, for excision of the jaw, or jaws, and for plastic operations about the face, the method gives greater facilities and freedom to the operator than any other plan I have tried. Mr. Appleby recommends the method also for prolonged dental operations." Buxton gives no figures on number of cases or number of disadvan- tageous results. Of the latter he says : "I have met with grave compli- cations, which, although in part due to the physical condition of the pa- tients, were undoubtedly not wholly independent of irritation caused in the intestines by the entrance of ether vapor." In a paragraph on after-effects he says : "Colicky pains in the intestines, urgent tenesmus, diarrhea sometimes dysenteric in character, painful distention of the intestinal tract with more or less severe collapse, are complications which have been recorded. Deaths have occurred." Unfortunately he does not state which of these have occurred in his own skillful hands. His method is practically identical with that advocated by Pirogoff, i. e., the generation of ether vapor by heat and its direct conveyance under its own power to the intestines. ^Cunningham and Leahy: Boston Med. and Surg. J., April 20, 1905. ^Dumont: Correspond.-Bl. f. schweitzer Aertse, 1903; ibid., 1904; ibid., 1908. ' Krugeline : Wiener Jclin. Woch., Dec, 1904. * Stucky: J. Am. Med. Assn., July 28, 1906. 'Lumbard: Med. Bee, Dec. 1, 1906. ° Buxton: "Anaesthetics," London, 1907. 436 ANESTHESIA An intercepter is used to prevent passage of liquid ether into the gut, and a temperature of not higher than 120° F. is recommended for the water bath in which the ether container is immersed. Leggett/ in 1907, reported a series of animal experiments and 13 personally conducted cases, which in the main gave satisfactory results. Leggett added to the Cunningham apparatus an outlet communicating with the vapor-carrying tube by a branched connection. This facilitated the relief at any time of intra-intestinal pressure. Dumont,^ in 1908, reported 4 cases, in all of which a smooth and satisfactory narcosis was maintained, practically without undesirable after-effects. The apparatus was a modification of that described by Dudley Buxton. Though commending it highly for suitable cases, Du- mont justly warns his readers that it is a method for exceptional cases; that it should be used only on properly prepared patients without intes- tinal lesions, and only by a skillful administrator. In the same year Anna Morosow ^ reported from the clinic of Pro- fessor A. Kadhan at St. Petersburg a series of 68 head and neck cases. Of these, 61 slept smoothly; in 5 narcosis was incomplete; in 2 surgical anesthesia could not be attained. The duration of anesthesia varied from 10 minutes to 2 hours and 45 minutes. Anesthesia was first induced by inhalation, and then maintained by the rectal method. The average con- sumption of ether for the induction and maintenance of anesthesia to- gether was 1.2 grams per minute; that for the period during which the rectal method was used 0.6 gram. Morosow observed that awakening was very prompt. Bloody diarrhea occurred in 1 case, blood-streaked stool in 5, abdominal pain in 3 cases, vomiting during narcosis in 3 cases. The apparatus used was essentially that of Pirogoff and Buxton, a temperature of 50° C. being recommended for the water bath. In 1909 Denny and Eobinson * recorded a series of 10 cases with gratifying results. In this year also Baum ° reported 8 cases anes- thetized with the apparatus of Pirogoff. Three cases showed ideal anes- thesia, 2 cases were restless, in 1 (an operation for epigastric hernia) distention greatly hindered the operator, and the patient became anes- thetized to a dangerous degree. In 2 other cases unfortunate after- results were observed. Both complained of abdominal pain during the induction of anesthesia, which lasted unusually long, and both showed marked abdominal distention. The first suffered after operation from profuse hemorrhage from the bowels (680 c. c. in 48 hours), while the * Leggett: Ann. Surg., Oct., 1907. ='Dumoiit: Ibid., 1908. 'Morosow: Buss. ArcMv f. Chir., 1908. * Denny and Eobinson : J. of Minn. Med. Assn., Feb. 1, 1909. = Baum: Zeit. f. Chir., 1909, No. II. ANESTHESIA BY COLONIC ABSORPTION OF ETHER 437 second died the morning after the operation and revealed at autopsy a gangrenous and perforated cecum and general peritonitis. Carson/ in 1909, reported a series of 18 cases, 2 of which were un- successful because of incomplete preparation. One of the remaining 16 cases, a large and muscular man who was delirious at the time, could not be anesthetized without the aid of a mask, which was used through- out the operation. One case had slight bleeding from the rectum. There were 2 deaths (an extensive face carcinoma, and a case of extreme hyperthyroidism). The author's apparatus was used. In July, 1909, Legueu, Morel and Yerliac ^ reported a series of ex- perimental cases, and expressed the belief that proper administration by this method is no more dangerous than that by inhalation. Oxygen was used as a vehicle for the ether-vapor, which was allowed to form at room temperature. In 1910 Sutton ^ published the results of a series of about 140 per- sonally conducted cases together with a description of the apparatus de- veloped in the course of the work and the technique used in the applica- tion of the method at Eoosevelt Hospital. About the same time, J. H. Cunningham, Jr.,* published his third article on the subject, giving the best review of the literature that had appeared up to this time. Shortly after this Thomas ^ published a description of an apparatus for rectal and pharyngeal anesthesia, which corresponds in principle al- most detail for detail with that described by Sutton (10 op. cit.). This author, however, provides for a continuous, or almost continuous, return flow of the ether-laden vehicle, somewhat after the manner described by Vidal ^ in 1906. The article deals exclusively with a description of the apparatus and direction for its use, making no reference to specific cases or to after-results. There are no citations to the literature. In August, 1910, Churchill ^ reported 47 cases anesthetized with the apparatus of Leggett. The range of age was from 6 months to 73 years. The time of anesthesia varied from 10 minutes to 2 hours, and narcosis was satisfactory to the operator in all but 7 cases. Two of these were herniotomies, in which anesthesia was complete, but in which the opera- tor was embarrassed by abdominal distention. Five could not be fully anesthetized — four because of insufficient preparation, one because of a leak in the apparatus. Alcoholic patients seemed to be more easily nar- cotized by this than by the inhalation method. Disturbance in the colon ^Carson: Interstate Med. J., Nov. 5, 1909, 16. ^Legue.u, Morel and Verliac: Compt. rendu Soc. iiol., June- July, 1909. "Sutton: Ann. Surg., April, 1910. * Cunningham: N. ¥. Med. J., April 30, 1910. ''Thomas: Tale Med. J., May, 1910. * Vidal: Presse medicale, 14, 1906. 'Churchill: Surg. Gynec. and Ohstet., 1910, 11, 2. 438 ANESTHESIA was observed in but one case, and only in the form of slight pain and blood in the stool 18 hours after operation on a patient who suffered be- FiG. 167. — Latest Form of Colonic Anesthesia Apparatus, a, Water jacket for vaporizing chamber; b, Drip cock for water jacket; c, Vaporizing chamber; d, Ther- mometer suspended in water jacket by metal clip; e, Metal tube carrying oxygen to spiral wier; f, Spiral wier; g, Chamber in water jacket for tubular heating-bulb; h, 4-way cock permitting administration of pure oxygen or oxygen-ether mixture; i, Outlet tube for ether-oxygen mixture; j, Afferent tube to colon; k, Tube connecting 4-way cock with spiral wier; 1, Tube from oxygen tank to 4-way cock; m, Glass tube forming terminus of efferent tube from colon; this tube is sealed only by immersion in water of cylinder "o"; n, Efferent tube from colon; o, Water manometer cylinder; the amount of pressure in the colon is determined by the depth to which the tube "m" is immersed; p, Oxygen tank; q, Carrying stand; r, Y-tube connecting rectal tube with afferent and efferent tubes; s, Short rectal tube with sphincter-bulb and multiple fenestrse. fore with hemorrhoids. Post-anesthetic nausea and vomiting were greatly reduced. Sanders/ in August, 1910, reported 11 cases. In 1, inefficiently prepared, the rectal tube became plugged after a half hour of satisfactory ^Sanders: Homeopath. Eye, Ear and Throat J., Aug. 1910. ANESTHESIA BY COLONIC ABSORPTION OF ETHER 439 anesthesia, necessitating resort to inhalation. In 1 staphylorrhaphy, chlo- roform was required by mouth during part of the operation. In several others momentary whiffs of chloroform were needed, and to supply this need Sanders added to Sutton's simple form of apparatus a Junker vial immersed in the same water with the ether container and receiving its supply of air from the same bulb as the latter. The Physiology of Colonic Anesthesia. — Theoretically the adminis- tration of any anesthetic should presuppose a full knowledge on the part of the anesthetist of the physiological action of the drug. Practically, however, in case of pulmonary anesthesia, this knowledge may be, and, in the vast majority of cases, is dispensed with in favor of an accurate knowledge of the symptoms of incomplete and of excessive narcosis, and of the practical means of correcting each. This knowledge, gained by extensive observation and supervised experience in the pulmonary method of administration, is not sufficient basis for the undertaking of adminis- tration by the colonic method. In the pulmonary method the drug is taken in by the automatic respiratory efforts of the patient, and is eliminated in the same way if pure air be substituted for the anesthetic mixture. No anesthetic-con- taining reservoir remains to continue imparting the drug to the blood plasma. Further, as the only means of elimination of the anesthetic is the same as the means of absorbing it, only so great an amount of the drug need be absorbed as is necessary to produce in the general circula- tion the required 14 of 1 psr cent for the narcotization of the central nervous system (cf. Overton ^). The absorbing surface of the lungs is so great and so well adapted to the purpose that a comparatively low con- centration of anesthetic vapor in the respired air is sufficient to produce the required percentage in the circulating blood. In the colonic method of administration all these conditions are changed. The drug cannot be taken in by the muscular action of the patient, nor can any unabsorbed excess be directly eliminated in that way. In the case of over-deep narcosis the unabsorbed residue of the drug must be evacuated by the active intervention of the operator. There must be considered in the use of this method the fact that the blood, after leaving the intestine with its load of ether, is obliged to pass through the lungs before reaching its goal in the central nervous system, and that in so doing a considerable portion of the contained ether will be eliminated into the air. The concentration of the drug at the ]Doint of absorption, therefore, may not be I/4 of 1 per cent of the pulmonary method, but 1/4 per cent plus the percentage necessarily lost by exhala- tion. Again, the absorbing surface of the colon is much smaller than that of the lungs, and the arrangement of the vessels j)erhaps less favora- ble to gaseous interchange, so that a higher concentration is required. ^Overton: Studien u. d. Narlcose, 1901, 185. 440 ANESTHESIA Each of these differences requires the intelligent attention of the anesthetist. Since the anesthetic mixture must be forced into the intes- tine, one is immediately confronted with the question of the proper de- gree of pressure to be used in the process. A sufficient degree must be employed to obtain moderate distention of the entire colon, else the avail- able absorbing surface will be too small. Too much pressure must not be exerted lest by overdistention the vessels of the gut be flattened out, circulation impeded or abolished, and absorption minimized, and the ischemic mucosa be left unprotected by its normal circulation to resist the irritant effects of the ether vapor. The contention may be raised that experiments in which narcosis has been produced by the use of high pressure are sufficient to disprove this statement. The error in this con- tention arises from the fact that excessive pressure breaks down the re- sistance of the ileocecal valve, as observed by Leggett on dogs, and by Lumbard ^ in the human subject, and that the narcosis is obtained by absorption under diminished pressure from the coils of the small intes- tine.^ The writer's attention was first directed to the necessity for the use of a moderate pressure by the repeated observation that reduction of pressure often resulted in deepening of the narcosis. The optimum pressure to be maintained in the colon has been deter- mined experimentally to be about 20 mm. of mercury, which is approxi- mately equal to the sum of the positive pressure in the intestinal capil- laries, and the negative pressure in the portal vein. This would be varied according to the blood pressure of the patient, i. e., should be reduced to 10 or 12 mm. in young children and may be increased in individuals with abnormally high blood pressure.^ On account of the inevitable loss of ether from the blood in its pas- sage through the lungs, it is sometimes necessary to adopt means, to be mentioned later, for keeping the respired air more or less laden with ether. For the same reason, because of the smaller and less efficient ab- sorbing area of the colon as compared with that of the lung, a relatively high concentration of the anesthetic mixture may be used. To meet this ^Lumbard: Med. Eec, Dec. 1, 1906. ^ In connection with this point it is important for those who make use of the colonic method of etherization to watch for symptoms of the so-called ' ' delayed ether poisoning" since from the foregoing it is plain that the liver — the great sufferer in this condition — is treated to a higher concentration of ether than in the same grade of narcosis from pulmonary administration. No case of thi9 kind has come to the writer's attention, however, unless the peculiar death men- tioned on page 455 has some affiliation with this class of cases. " In connection with this question it is well to have in mind the experiments of Quirin, in one of which a normal healthy cat having a blood pressure of 85 mm. died after 5 minutes of an intra-abdominal pressure of 10 mm. Deutsch. Arch. f. Uin. Med., 1901, 21, 79. ANESTHESIA BY COLONIC ABSORPTION OF ETHER 441 last requirement, a number of early investigators and, unfortunately, some recent ones adopted the expedient of passing pure ether vapor into the gut under the pressure incident to its generation. This doubly dangerous procedure has resulted in a number of deaths, in one of which (reported by Professor Baum) autopsy showed a gangrenous and per- forated cecum and general suppurative peritonitis. The danger of too great concentration of ether is obviated in the method used by Sutton, by employing oxygen (or air) as a vehicle and by keeping the ether from which the vapor is derived well below its boil- ing point. By maintain- ing a uniform tempera- ture in the ether, with a fairly constant flow of oxygen and a definite period of association of the oxygen stream with the liquid ether, a fairly constant degree may be attained. Development of the Method. — From the con- siderations Just reviewed it is apparent that the history of the develop- ment of this method of ether administration is intimately associated with that of the develop- ment of the apparatus employed. Pirogoff used an ether container im- mersed in a water bath at a temperature of 120° P., with a rubber tube to lead the pure ether vapor into the rectum. An almost exactly similar apparatus was used by Buxton, Baum, Dumont, Kadjan, and Morosow (Fig. 168), as well as in the cases reported by Bull, Weir, and Post. Cunningham, of Boston, made the first great advance by using a water bath of a temperature below the boiling point of ether, and by car- rying the vapor of the latter into the intestine in a vehicle of air. (Mol- liere had previously used a hand bellows to force the ether vapor into the intestine, but ^dthout admixture of the air.) In the Cunningham apparatus no provision was made for emptying the distended intestine, this being accomplished when necessary by inserting the finger of the anesthetist through the sphincter ani alongside the rectal tube. Vidal added to the apparatus a provision for a continuous return flow of gas from the rectum, and a year later Leggett added to the Cun- ningham apparatus an exhaust tube which could be opened when it was Fig. 168. -Apparatus for Administering Ether PER Rectum. (Buxton.) 442 ANESTHESIA desired to empty the intestine, but which remained closed in the interval. In July, 1909, Ligueu, Morel, and Verliac (Fig. 169) first reported the use of oxygen as a vehicle for ether vapor ^ in rectal anesthesia. The work of these writers was confined to animal experimentations. The apparatus (Fig. 170) of Leggett represented the "state of the art" at the beginning of Sutton's series of cases, and, with the exception Fig. 169. — Appahatus of Ligueu, Morel and Vbhliac. of the U tubes, was essentially the apparatus used in the earlier work. In a number of these cases it gave entirely satisfactory results ; in others, obstacles were encountered which made difficult, or even prevented en- tirely, the attainment of satisfactory surgical narcosis. The study of A- OtAtuATfO SI*" CfUVOtK Z'lXo' S-*>' '■*!. CYUnBU\ t'tlS' \C-^L»*» yviivOow /'/v 3. X.iMiLt HvDeti snpP£H ivMiwntr^. ^ ?-C4^0 7UQL JfJ^/vvz/vft THIKBUQH SnPfe^'i* H-tinAUST-nj^e. -ratMfrf ttetTunn. • K-ct-umP To 7tcac/(./tr£ -rvac H. L- HAMttWm tr cyuNBCR ■». H. ircv ««£K To CMPry "B. T- RunQt-n ruae. rucm y 7v it<mijj,ji.JiJJJ/Jl^,J>^'->'JJJ^^-''-'-'J---^' ZZ ANESTHESIA BY COLONIC ABSORPTION OF ETHER 447 safety valve, would put a dangerous pressure on the gut. When such excessive pressure has subsided, the mercury falls back from the upper chamber of the manometer, and the safety valve is closed. The H-tube e makes it possible to have, at the same time, means of passing either oxygen or air through the genera- tor and also of inflating the intestine with pure oxygen or air without appreciable admixture of ether. This latter procedure is accom- plished by simply open- ing the pressure clip d, which allows the oxygen or air to pass into the afferent tube and on into the intestine without making its way through the generator itself. The generator may be hung by a bracket from the oxygen tank, as shown in Figure 176, or set upon a small table. For those who wish to make their own apparatus, a simpler form of Fig. 174. — Sectional View of H-Tube. ac, afferent connection; ec, efferent connection; rtc, rectal tube connection; br, brace. \^^. ipaSS Fig. 175. — Simple Form of Sutton's Apparatus. Manometer not shown. generator will be found quite satisfactory. This may be made by the use of the spiral wire in any wide-mouthed bottle capable of containing 250 to 400 grams of ether and 4 or 5 inches of free space between the fluid and the cork. The manometer is inserted through the cork and the proper afferent connections provided. In the place of the water jacket, a pail of warm water is provided, and the bottle partly immersed in it. The temperature is registered by a floating thermometer, and is kept ANESTHESIA BY COLONIC ABSORPTION OF ETHER 449 up to the proper point by occasional additions of very hot water. (Fig. 175). The Afferent and Efferent Tube Systems. — These, as will appear from a glance at Figs. 176 and 179, run a parallel course for the greater part of their length — the efferent or exhaust tube being led to the head of the table in order that it may be controlled by the anesthetist sitting there. The afferent tube is of small caliber, since it conveys only gas, while the efferent tube, which is frequently called upon to conduct water and semi-fluid feces, must have greater inside diameter. Both tubes have very thick walls in the portion which passes over the edge of the table and under the patient's thigh. This is to obviate the danger of com- pression in this situation. The rectal tube is a short single tube having a bulb about 3 inches from its outer end supplied with 5 to 7 fenestras. This bulb in use aids in the prevention of leakage in case of a lax sphincter, while the multiple fenestras are a safeguard against closure of the tube due to prolapsed mucosa or to fecal particles when the exhaust tube is opened. Communication between the rectal tube on the one hand, and the afferent and efferent tube system on the other, is estab- lished by the use of a Y-shaped tube (Fig. 174) of glass or metal, which stands horizontally between the patient's thighs, close to the anus. The upper straight arm connects with the afferent tube while the lower curved branch leads to the efferent connection. By reason of its position and construction, this Y-shaped tube acts as a trap to catch either con- densed ether from the afferent tube or semi-fluid matter coming from the rectal tube when the exhaust is opened. A strong glass tube is introduced into the efferent system, as shown at ee, Fig. 176. This serves the double purpose of preventing a sag in the exhaust tube at this point and of furnishing a rigid support for the slid- ing hooks a, which form the principal means of attaching the apparatus to the table. The ends of the efferent or exhaust tube are immersed in a few inches of water in the bottom of a wide-mouthed bottle, which sits on the floor under the head of the table, or in the drip pan con- nected with the latter. This bottle serves both as a collector of any fluid return from the intestine and as a "tell-tale," since the amount of gaseous return following the opening of the exhaust is readily appreciated when it is seen or heard bubbling through the water. Continuous leakage from the exhaust is prevented by a spring clip lih, which is modified, as shown in Fig. 177, so that the afferent tube is held in relation with one of the finger rests of the clip. This relation of clip and afferent tube in- sures the closure of the latter by the same finger pressure which opens the former. Gas is thus prevented from entering the intestines as long as the exhaust is open. For the sake of keeping it in a definite position, this combination clip is attached to the table by a long wire hook. Since, in some cases, it is necessary temporarily to supplement the colonic ad- 450 ANESTHESIA ministration by the addition of ether by mouth, a T-tube, bb, Fig. 176, is placed in the afferent system close to the generator, and a small rubber tube is led off and closed by a spring clip. In mouth and throat cases, where it is desirable for the patient to retain an active coughing reflex, it has proved of advantage to introduce a small mica-plate check valve beyond the origin of the accessory mouth Fig. 177. — Combination Clip with Hook. ^777777^/^'^/^^}///^//// [^ [-v.v.,v///^^W^^ '^^^^';^'i?y,r^ ™"'*bss^?'^ tube. Coughing produces a very marked increase in intra-abdominal pressure, and in some cases before the introduction of this valve a paroxysm of coughing has resulted in the driving of fecal-stained fluid back into the generating chamber. With the check valve, as shown in Fig. 178, this cannot occur. When violent coughing is permitted, it is necessary to open the exhaust during each paroxysm, lest the rectal tube be extruded by the effort ; or an automatic safety valve may be arranged by leaving off the spring clip and immersing the distal end of the exhaust tube in about 18 inches of water. (Fig. 179.) This height of water will be sufficient to prevent escape of gas at 20 mm. pressure, but readily permits escape at the higher pressure incident to coughing. When this device is used the intes- tine may be emptied of gas by simply raising the end of the exhaust tube to the surface of the water. Technique of Method. — Preparation of the Patient. — One of the most important consider- ations, as observed by all workers with intestinal anesthesia, is the thorough cleansing of the colon. This is accomplished by a cathartic (castor oil) given the night preceding the operation and followed in the morning by high soapsuds enemata re- peated until the return is clear. In Sutton's cases three enemata, 1% to 2 hours apart, were regarded as the minimum number. In alcdholic and very muscular subjects, and in operations on the mouth or upper respira- tory tract, it has been found useful to give 1/6 to 14 grain of morphin Fig. 178. — Check Valve Used on Afferent Tube When Coughing is to be Permitted. (Partial sectional view.) thb, thick walled brass tube con- necting with generator; tb, thin-walled brass tube —notched on end toward valve — connecting with main afferent tube; gt, glass tube surrounding valve chamber; mp, mica-plate valve; re, cuffs of rubber tubing connecting glass and brass tubes. ANESTHESIA BY COLONIC ABSORPTION OF ETHER 451 and 1/120 to 1/100 grain of scopolamin hypodermically 1 hour before operation. The Administration. — Before the patient is brought to the etheriz- ing room, the anesthetist affixes the apparatus to the table, as shown in Fig. 179, except that the rectal tube is not attached and the Y-tube and its connections are allowed to hang down at the side of the table, while the accessory mouth tube is permitted to hang from the side of the gen- erator. The ether reservoir is charged, the water jacket is filled with Fig. 179. — Sketch of Pipe-Line System with Safety Valve Water Manometer At- tached. Note that combination clip is not used with this arrangement. water at about 90° F., and the electric lamp is connected with a plug in the wall, hut not lighted at this time. The end of the exhaust tube is placed in the "tell-tale" bottle under the table. • The anesthesia is then started by the pulmonary method, and carried to a stage of partial relaxation, when the patient is brought to the operat- ing room and placed on the table. The rectal tube, well greased, is then quickly inserted until the bulb lies just inside the sphincter, the anes- thetist before starting the initial anesthetic having protected his left hand with a rubber glove. The patient's left thigh is then raised, and the branch tube brought under it to its proper position and connected with the rectal tube. For this brief period the cone has been held over the patient's face by a nurse. The anesthetist then removes his rubber glove, takes his place at the patient's head, and slowly turns on the oxy- gen. As soon as this is done the cone may be removed from the patient's face. If the operation does not involve the patient's mouth, it is best to cover this, and, if possible, the nose as well, with three or four large sterile towels which, by causing a certain amount of rebreathing, im- pede the elimination of ether from the lungs. If, during the change from the pulmonary to the colonic method, the patient has "come out" and begun to make troublesome voluntary movements, he can be quickly "put under" by admitting ether vapor to the space under the towels through the accessory mouth tube. 452 ANESTHESIA As soon as pressure in the colon has been raised to the required 20 mm., the exhaust should be opened and the gut allowed to empty itself. This process of filling and emptying the intestine should be repeated three or four times in order to eliminate as thoroughly as possible the natural gases of the bowel. The needle valve of the oxygen tank is then set at a point which just maintains the required 20 mm. pressure, and usually demands little or no further adjustment during the rest of the operation. If the patient tends to come out from the influence of the anesthetic, the bowel may be emptied from time to time to carry out any intestinal gases which tend to dilute the anesthetic mixture. If, on the other hand, the anesthesia continues sujfficiently deep, no further use of the exhaust need be made until the end of the operation. This is be- cause the oxygen is absorbed by the bowel with the same ease as the ether vapor, in fact, more rapidly, so that no residue of the anesthetic remains. When air is used as a vehicle, the bowel must usually be emptied every 5 or 10 minutes, as in this case a nitrogen residue tends to accu- mulate and to act as a diluent of the freshly added anesthetic mixture. Whenever possible, oxygen should be used instead of air as a vehicle. The reasons for this, are: (1) It reduces the dangers of anesthesia; (2) it greatly diminishes the rapidity and depth of respiration, in some cases even causing the phenomenon of apnea or hyperoxygenation, thus greatly reducing the loss of ether through the lungs; and (3) it obviates the necessity of the frequent use of the exhaust, and hence contributes to the smoothness of the anesthesia and the comfort of the anesthetist. In the ordinary ease, a smooth anesthesia continues from this point with little further active intervention on the part of the anesthetist. The thermometer must be watched to see that the temperature of the water bath does not become too high. When the temperature tends to rise above 90° F., the incandescent lamp may be partly withdrawn from the Avater bath, or it may be turned off for a few minutes, being lighted when the temperature has fallen to 88 or 89° F. If, with a lighted 10 candle power lamp inserted the full length of the Avater jacket, a tem- perature of 90° F. cannot be maintained, it is certain that there is a leak in the apparatus or from the patient's sphincter, necessitating an exces- sive flow of the mixture of oxygen and ether vapor to maintain the re- quired pressure. Too shallow narcosis is met by adjusting the face towels so as to cause increased rebreathing of the exhaled ether (this does not cause cyanosis on account of the constant absorption of oxygen from the bowel), and, if this is not sufficient, by introducing the anesthetic mixture under the towel from the accessory tube. Too deep narcosis is met by temporarily shutting off the stream of ANESTHESIA BY COLONIC ABSORPTION OF ETHER 453 oxygen and allowing the exhaust to remain open for a short time, or by markedly reducing the pressure without opening the exhaust. The depth of narcosis is determined by the pupils, which are usually at maximum contraction in complete anesthesia by this method (unless morphin and scopolamin have been administered, when they have little value) ; by the degree of muscular relaxation, and by the color which may be noted from the lips and face, but better from the color of the blood in the wound. The character of the respiration is of less value, as the patient may have excellent color, though breathing very infrequently. Short, shallow, jerky respiration, especially when associated with a dusky color, is a danger sign, just as it is in the pulmonary method. The writer rarely takes the pulse except in cases which are mani- festly doing badly or where cardiac complications are known or sus- pected. Muscular tone is best determined from the tension of the jaw muscles and from the presence of voluntary movement of the tongue. It is the writer's habit to keep one finger in the patient's mouth in order to detect the first active tightening of the jaw or voluntary movement of the tongue. Sufficient ether need not be given to make the lower jaw entirely relax, but merely enough to prevent actual biting of the finger. Difficulty in breathing is readily overcome by extending the head on the neck by simply pulling with the finger upon the upper incisors. This has always been sufficient, so that in the entire series of cases here re- ported neither mouth gag nor tongue forceps have been used to improve the respiration of the patient. At the end of the operation the bowel is filled with oxygen to a pres- sure of 20 mm. and emptied several times, these "oxygen enemata" serv- ing to carry off the greater part of the unabsorbed ether. Occasionally it seems advisable to massage the abdomen in the direction of the colon before removing the rectal tube^ but this is not usually necessary. The rectal tube is then withdrawn and disconnected from the Y-tube. After-treatment. — As soon as the patient is returned to bed a high soapsuds enema is given, being siphoned off after a few minutes if neces- sary. This treatment is repeated a half hour later. Vomiting is usually absent; when present it is very rarely severe, the patients, curiously enough, disclaiming any feeling of nausea. Eecovery is rapid. The possibility of the transmission of typhoid, amebic colitis, or other intestinal infection from one patient to another is prevented by keeping the rectal tube and the Y-tube in a 1 per cent solution of forma- lin between operations. The glass tip of the accessory mouth tube, when not in use, is kept in the same solution. Discussion of Cases. — Up to the present time the writer has adminis- tered ether by this method to about 140 cases on the surgical service of Eoosevelt Hospital. Of this number careful records were taken of the first 100 cases. Of the remaining 40, mostly private eases, no detailed 454 ANESTHESIA records have been made. It may be said, however, that all were satis- factory and that untoward results occurred in none. In only one case — the second of the series — was an attempt made to administer the anes- thetic per rectum from the beginiiing. This proved so slow, and was so uncomfortable and distasteful to the patient, that after about 20 minutes a cone was used to complete the initial establishment of the anesthesia. Inasmuch as there is no real indication for beginning the administra- tion by rectum, the writer has never made a second attempt to do so. Of the 100 cases in the recorded series, 91 were ward patients and 9, private patients. The age range was 2 to 77 years. The operations were as follows: Tumors, glands, etc., of neck 31 Amputations of breast 9 Goiters and thyroglossal cysts 8 Craniotomies 6 Corrections of old fractures of limb 5 Resections, sutures and osteotomies of inferior maxilla • 5 Partial excision of the tongue 4 Staphylorrhaphy 4 Tracheotomy 3 Mastoid 3 Inguinal hernia ■ ■ ■ 2 Removal of parotid tumors 2 Resection and osteotomies of superior maxiUa 2 Removal of Gasserian ganglion 2 Skin grafting 2 Orchidopexy Hydrocele Appendectomy Nephrotomy Ludwig's angina Enucleation of eye Resection of knee , • . Cervical laminectomy Axillary adenitis , Excision of sternomastoid Plastic for strictures of esophagus Laryngectomy Neuorrhaphy The longest operation of the series consumed 2 hours and 20 min- utes; the shortest, 5 minutes: the average time being 53 minutes. The average consumption of ether was 87 grams per hour in the 64 consecutive cases in which record of this point was kept. Twelve of the 100 patients had preliminary injection of morphin and scopolamin. ANESTHESIA BY COLONIC ABSORPTION OF ETHER 455 In 25 cases, oxygen was used as a vehicle for the ether vapor. Forty-three patients had at some time during the operation a supple- mentary administration hy mouth of ether or chloroform. In 12 cases, there was eructation of gas, prohahly indicating the pas- sage of the gas into the stomach from the distended small intestine. Of these only 4 occurred in the 71 cases following the adoption of a 20 mm. maximum pressure in the bowel. In only 18 cases was there any perspiration, and in none of these was it profuse. Forty-three patients vomited or regurgitated stomach contents after operation; of these, several disclaimed any sensation of nausea. Twelve had abdominal pain. Five had bloody stools or blood-streaked return from the post-anes- thetic enemata. All cleared up in from a few hours to 3 days, and in none was the loss of blood accompanied by noticeable weakness or ab- dominal pain. The most severe of the cases continued to pass small quantities of blood for 3 days, during which the patient also vomited persistently. This patient. Case XXVI of the series, was the last save one in which any hemorrhage (beyond the negligible amount occasionally caused mechanically by the rectal tube) has occurred. Case XCVII, as an incident to the Introduction of a new form of ether evaporator, was treated to an excessively concentrated vapor, so that great care was necessary to prevent narcosis from becoming too deep. In the first 3 days following the operation this patient had 5 bloody stools. He felt no discomfort, however, and was discharged on the fifth day in perfect general condition. In the series of cases to date there have been 5 deaths from all causes. In none of these, in the judgment of the operating surgeon, was the method of administering the anesthetic a contributing factor. A brief statement of the conditions in each of these cases follows : Case I. — Large, heavy man, moderately alcoholic. Operation, partial excision of the tongue for epithelioma. Patient somewhat blue; pulse small and rapid throughout operation. Died, apparently of operative shock, about two hours after return to ward. Case II. — Large, heavy man. Age 35. Moderately alcoholic. Oper- ation, tracheotomy and removal of cervical glands as a preliminary to laryngectomy for carcinoma of larynx. Anesthesia was "shalloV throughout, patient coughing and groaning frequently. Made prompt ether recovery, but died 2 days after of pneumonia. Case XXV. — ^^Fairly well-nourished man; age 53; moderately alco- holic. Operation, hemi-excision of the tongue and removal of right cer- vical glands for epithelioma. Patient took initial anesthetic slowly, and was markedly cyanotic. Color and general condition improved after be- ginning of the administration per rectum. Anesthesia was shallow 456 ANESTHESIA throughout, patient swallowing frequently. Late in the operation there was a markpd hemorrhage, and shortly afterward — 1 hour and 35 min- utes after the beginning of the operation — ^the patient died. Case XLIY. — Muscular man, age 24; brought to hospital almost moribund with compound depressed fracture of skull. After operation lasting 35 minutes, the patient left the table improved, but never re- gained consciousness and died 2 days later. Autopsy showed extensive fractures of vault and base, extensive lacer- ation of brain, and marked subdural and epidural hemorrhage. The colon was normal, showing no injurious effects from the ether. Case XLYII. — Slender negro, age 31; brought to hospital in ambu- lance with extreme dyspnea of sudden onset. Operation, low trache- otomy, with patient in sitting posture on account of orthopnea. On ac- count of this position the rectum was compressed by the weight of the upper bowel, and introduction of ether vapor and oxygen into the colon was almost impossible. The operation gave little relief, but ether recov- ery was satisfactory. Dyspnea and cardiac weakness progressively in- creased, and two days later the patient died. Autopsy showed a large false aneurysm of the descending arch of the aorta. Colon normal. One other death has occurred in Eoosevelt Hospital from the adminis- tration of ether by this method. Another member of the interne staff administered the anesthetic in this instance, but the case came under the writer's observation both during and after the operation. The patient was a well-nourished child, five years of age, who had been anesthetized on two previous occasions for the correction of harelip and the removal of adenoids. The operation in question was a staphy- lorrhaphy lasting about 50 minutes. Throughout the operation there was noticeable difficulty in maintaining a smooth narcosis, the latter being too deep and too shallow by turns. In the course of the shallow inter- vals a little chloroform was given several times on a "sponge stick." There was no excessive loss of blood. Toward the close of the operation the patient's color became very bad, and the pulse small and rapid. She was hurried to the ward, stimulated, and given external heat. In the course of a half hour she became restless and talkative, calling for water and asking to be taken home, but apparently recognizing no one about her. She did not vomit. The pulse continued rapid and small, and an intravenous infusion was given with slight temporary benefit. After this she gradually relapsed again into unconsciousness, and about two hours after operation she died. Unfortunately an autopsy was not permitted. It is the writer's belief that this method, safeguarded by such im- proved apparatus as that described, and by the use of oxygen as a vehicle for the ether vapor, is one of extreme safety in the absence of definite intestinal lesions. ANESTHESIA BY COLONIC ABSORPTION OF ETHER 457 Conclusions. — The colonic method of administration of ether is more complex than the pulmonary method in general, and requires from the anesthetist a broader appreciation of the physiological factors involved. For these reasons alone its field of usefulness is limited to cases in which it presents distinct advantage over the pulmonary method. It is, there- fore, not a method adapted to the experimental use of the tyro, hut rather a valuable addition to the armamentarium of the trained anes- thetist. We may summarize the indications and contra-indications as follows : Indications. — (1) Operations upon the respiratory tract (head, neck, and chest), especially such as lay open the mouth, larynx, pharynx, and trachea. (2) Operations upon patients in whom absorption must be minimized on account of lung, heart, or kidney lesions. (3) Operations upon patients already suffering from respiratory embarrassment. CoNTKA-iNDiCATiONS. — (1) Operations upon patients presenting lesions of the alimentary tract, especially such as might cause weakness of the wall of the colon. (2) Laparotomies in general, except such as do not open the general peritoneal cavity, e. g., suprapubic cystotomy. This is because of the interference of the inflated colon with the work of the surgeon. (3) Operations upon patients with markedly incompetent sphincter ani or with large fistula in ano. A patient with an open appen- dicostomy would offer the same difficulty of leakage. (4) Operations upon patients suffering with orthopnea. In these cases it may be impos- sible to inflate the colon because of the obstruction caused by the weight of the other viscera resting upon it. (5) Emergency cases in general, because of the lack of preparation of the colon. Advantages. — The points in favor of the method in cases in which its use is indicated may be summed up as follows : (1) Freedom of ope- rative field from contamination by the anesthetist. (2) Ability to main- tain a smooth and continuous anesthesia in operations involving the respiratory tract, thus shortening the time and reducing the shock of operation. (3) Uniform depth of anesthesia, causing light narcosis and marked saving in ether. This saving is much greater when oxygen is used as the vehicle. (4) Lessening of pharyngeal and bronchial secre- tion, and of tonic contraction or troublesome relaxation of jaw muscles. (5) Ability to administer oxygen without interruption of anesthesia. (6) Minimized loss of heat during operation because of diminished sweat- ing and ether refrigeration. (7) Eeduction of post-operative vomiting and nausea. Disadvantage. — The only point against the method in cases where its employment is indicated is the occasional difficulty in maintaining profound anesthesia without the use of the supplementary mouth tube. PAET II OIL-ETHER COLONIC ANESTHESIA History. Animal Experiments. Eemarks on the Method. Preparation of the Patient: Preliminary Medication. Administration. Control of the Anesthesia. Physiology. Illustrative Cases. History. — The original work of Cunningham and Sutton's careful record of cases were prominent factors in the development of oil-ether colonic anesthesia. (See Part I of this Chapter for a history of rectal anesthesia.) In 1913 at the Seventeenth International Medical Congress in Lon- don, the senior author read a paper on Oil-ether Anesthesia. The ex- perimental animal work was completed just previous to this date. The practical clinical work with oil-ether was begun at the People's Hospital, and the first successful administration was in September of 1913 to a patient of Dr. I. M. Rothenberg, his brother operating. The work was completed at Columbus Hospital and was successfully demon- strated at other hospitals in ISTew York City, then in neighboring cities. Animal Experiments. — All of the experimental laboratory work was conducted under the immediate supervision of Professor Wallace, of the pharmacological department of the University and Bellevue Hospital Medical College. In studying the anesthetic value of ether introduced in solution into the rectum, about twenty-four experiments on dogs were performed. The method generally employed was as follows: Several hours before the administration of the ether a saline cathartic was given by a stomach tube; half an hour before, a subcutaneous injection of morphin sulphate (from 0.001 to 0.03 gm.), and immediately before, a cleansing enema of soap and water. The animal was then placed on its back on a holder, and a fairly stiff rubber catheter was inserted into the rectum and pushed up the colon for a distance of about ten inches. The ether solution was placed in a bottle with an outflow tube at the bottom attached with rubber tubing to the catheter. The bottle was then raised to any desired height, from one to six feet, and the flow regulated by a screw clamp on this tubing. 458 ANESTHESIA BY COLONIC ABSORPTION OF ETHER 459 In the first experiment performed, a five per cent ether solution in normal saline was used. About 500 c. c. of this solution was slowly in- jected into the colon. A very mild excitement stage ensued, and com- plete anesthesia continued for thirty minutes, gradual recovery then taking place. There was a watery discharge from the rectum during the recovery stage, but no diarrhea on the following day. This experiment was repeated on a second dog under the same conditions, but complete anesthesia was not obtained. I next suggested oil-ether, with the idea of reducing the bulk. Ether is miscible in all proportions in oil. The oil also prevents irritation, and its great affinity for ether prevents a too rapid absorption of the latter; furthermore, when the oil-ether mixture is in the colon, as the ether leaves the oil in gaseous form, heat is ex- tracted from surrounding parts, including the oil-ether mixture and the colon. This cooling checks both evaporation and absorption, and regu- lates the doses at all times. The difference between the slow absorption from the colon and the rapid elimination from the lungs is the third factor that assists in automatically regulating the anesthesia. Experiments under the supervision of the junior author were then made to discover if there was any difference in time in the ether separat- ing from the oils. The oils used were olive, cotton-seed, cod liver, neats- foot, paraffin oils, and Russian mineral oil; also milk and cream. The same quantity of ether and of the oils was placed in separate test tubes and put in a water bath kept at a temperature of approximately body heat. No difference in time was found in the separation of the ether from the different oils. The experimental procedure with animals was then changed in that the ether was given dissolved in oils and in greater concentration ; in one experiment in which 100 c. c. of ether in 250 c. c. of olive oil (i. e., forty per cent) was inserted into a dog of 10 kg., the animal became com- pletely narcotized in one hour, when the whole solution had been in- serted. The anesthesia persisted, with a good pulse and regular, deep breathing for forty-five minutes, when the breathing became short and irregular. The respiration gradually became weaker and stopped fifteen minutes later. No effort was made to save the animal. This dog had received a large amount of morphin preliminary to the ether. In two other experiments in which no morphin was given, one dog (weight 6 kg.) received 150 c. c. of a 40 per cent ether solution, and one (weight 6 kg.) 190 c. c. of 40 per cent solution. In neither was complete anes- thesia obtained. In the remaining experiments the ether was given in solution in oil from 55 to 75 per cent the amount of ether injected being from 50 to 75 c. c. Ten successful experiments were carried out, with complete anesthesia and no alarming symptoms. The shortest time required for surgical anesthesia was five minutes, the longest fifty. The duration of anesthesia after the ether insertion 460 ANESTHESIA was stopped averaged about an hour, except in cases in which the colon was washed out, when recovery set in more promptly. In no case has there been any evidence of more than a mild irritation of the gut follow- ing the. ether introduction, and this, when present, has disappeared within twenty-four hours. A flushing of the colon with a large amount of fluid has shortened the duration of anesthesia, and the subsequent injection of oil prevented or lessened rectal irritation. The following is the record of an experiment : Dog, weight 12 kg., given 10 gm. magnesium sulphate in 100 c. c. water by stomach at 10 :30 A. M. Morphin sulphate, 0.02 gm. at 3 :20 P. M. Eectum washed out at 3 :30 P. M. At 3 :45,.125 c. c. ether solu- tion (75 per cent in cottonseed oil) injected into colon at a pressure of 20 mm. Hg. At 4:01, complete anesthesia, with no preliminary excite- ment stage. At 4 :05, rectum washed with water. At 4 :10, recovery be- ginning. At 5, animal able to run about. Slight diarrhea during night and following day. Remarks on the Method. — One of the underlying thoughts in evolv- ing oil-ether anesthesia is to avoid certain dangers that pertain to in- travenous anesthesia. The only apparatus needed are a small catheter, a funnel to hold the mixture, and a measuring cylinder. On account of the gradual and equal absorption of the ether from the colon, and of its rapid evaporation from the lungs, it is a comparatively safe anesthesia, provided the same care and attention are given to details as with any inhalation anesthetic. Mucus and saliva are absent, and the patient's lungs and stomach are spared. As yet only ether has been experimented with. The preparation of the patient should be the same as that for ether- vapor anesthesia by rectum. This is most important and is as follows : Preparation of the Patient. — A cathartic of castor oil should be given the night preceding the operation, followed in the morning by warm water enemas one hour apart until the return is clear. The pa- tient should then be allowed to rest for two to three hours. Preliminary Medication. — One hour before the introduction of the mixture, 5 to 20 grains of chloretone in a suppository or dissolved in 4 drams of ether and mixed with an equal amount of olive oil are given per rectum with the patient in the Sims position. Both the preliminary and the mixture should be administered very slowly through a funnel which is attached to the end of the catheter which has been well lubri- cated and inserted 4 inches into the rectum. As paraldehyd mixes with oil and ether in all proportions, it may be found that two to four drams of paraldehyd with an equal amount of olive oil and given' alone is preferable as a preliminary. As isopral, like chloretone, has a slight local analgesic as well as general hypnotic effect, this drug may possibly prove to be superior as a preliminary to the others mentioned. Thirty minutes after the chloretone or paraldehyd has been ANESTHESIA BY COLONIC ABSORPTION OF ETHER 461 given, one-twelfth to one-quarter of a grain of morphin with 1/200 to 1/100 grain of atropin is given hypodermatically. For alcoholics and athletes the following is suggested: Two hours before operation give 1/100 grain of hyoscin hydrobromid hypodermatically and one hour be- Ty ^3? ^Z7 idyd) — a state of profound unconsciousness. In some instances, witii heavy dosage, an analgesic agent injected into the subarachnoid space may produce a state of mental lethargy bordering upon that which follows the inhalation of an anesthetic agent, with the loss of all forms of sensa- tion — a real anesthesia. As a rule, however, with moderate dosage, the analgesic agent introduced into the spinal canal gives rise only to anal- gesia — loss of sensibility to pain. Tactile sense, the sense of heat and cold, of pressure and of traction, are not completely destroyed in the latter case. The operator who fails to bear in mind the above differentiation is apt to experience more or less difficulty at times, and to feel that he has a right to chronicle dissatisfaction or failure with the method under dis- cussion. It has been our purpose to give, as briefly as possible, in the pages which follow, a cursory review of the work of others, rather than to con- fine ourselves strictly to the limits of personal experience. With spinal analgesia, as with every other form of analgesia or anesthesia, the method has its enthusiastic adherents and its uncompromising opponents. We have endeavored, in the light of personal experience, to examine the evi- dence pro and con, and to give a fair and impartial statement of our findings. HISTORY The history of spinal analgesia may be divided, for purposes of con- venience, into four periods, which are more or less overlapping in time and achievement: (1) Discovery of and experimentation with cocain; (2) experimentation with cocain from the neurological point of view, with regard to its analgesic effects upon sensory nerves, including the spinal cord; (3) application of the analgesic effects of cocain upon the cord to surgical operations below the diaphragm; (4) extension of the application of spinal analgesia to parts of the body above the diaphragm. Experimentation with other agents. Discovery of and Experimentation with Cocain.— The discovery by Niemann, in 1859, of the alkaloid of coca leaves, to which the name cocain was given, may be said to mark the first event in the history of spinal analgesia. The discovery by Schraff', in 1862, of the local analgesic properties of this substance when placed upon the tongue was the second step forward in the history of this method. With the application of the latter discovery to surgical purposes, sug- 556 ANESTHESIA gested by Koller,^ in 1884, the history of spinal analgesia was fairly in- itiated. Following immediately upon these discoveries and their announce- ment,2 many experiments were undertaken by investigators throughout Europe and America, all having for their motive the production of local analgesia for surgical purposes. This particular phase of the general subject of anesthesia falls within the scope of the chapter on local anal- gesia. It concerns the history of spinal analgesia only in so far as the discovery and application of cocain by others led to the sequence of de- ductive reasoning by Corning, and furnished the means for the applica- tion of the theories by which he gave to the world the discovery of spinal analgesia. Experimentation with Cocain from the Neurological Point of View with Regard to Its Analgesic Effects Upon the Sensory Nerves, Including the Spinal Cord. — Coming's brilliant work ^ on the prolonga- tion of the analgesic effects of cocain subcutaneously administered v/as the logical antecedent to his equally brilliant experiments with the local medication of the cord.* In his first paper on spinal analgesia Corning was influenced in his deductions by the work of Harley,'^ who showed that a poison sijch as strychnin, injected under the membrane covering the cord, "can act only through the intermediation of the blood vessels, since, when the latter are separated from the cord, the solution remains entirely inert." Corning concluded from this that, "in order to obtain the most im- mediate, direct, and powerful effects upon the cord with a minimum quantity of a medicinal substance, it is by no means necessary to bring the substance into direct contact with the cord; it is not necessary to inject the same beneath the membranes, as in the case of the frogs, since the effects are entirely due to the absorption of the fluid by the minute vessels. On the other hand, in order to obtain these local effects, it is first necessary to inject the solution in the vicinity of the cord; sec- ^ Roller, Karl : ' ' On the Use of Cocaine to Anesthetize the Eye, ' ' Wiener med. Woch., Oct. 25, Nov. 1, 1884. Translated by H. Knapp: "Cocaine and Its Uses in Ophthalmic and General Surgery." Putnam's Sons, N. Y., 1885. ^ Noyes, Henry D. : "A Few Cursory Notes on the Proceedings of the Meet- ing of the German Ophthalmol ogical Society, Held at Heidelberg in the Middle of September of This Year." Med. Bee, Oct. 11, 1884. ^Corning: (1) "On the Prolongation of the Aneesthetic Effects of the Hydrochlorate of Cocaine When Subcutaneously Injected. An Experimental Study." N. Y. Med. J., Sept. 19, 1885; (2) "The Author's Method of Local Ansesthetizatipn by Incarceration of the Anaesthetic in the Field of Operation, ' ' Part II, "Local Anaesthesia," 34. * Corning : ' ' Spinal Anaesthesia and I'ocal Medication of the Cord, "A. Y. Med J., Oct. 31, 1885, Eeprinted, 1909, 72, 790. Also in "Local Anaesthesia," 85. ''See Ringer, Sidney: "A Handbook of Therapeutics," 1870, 387. SPINAL ANALGESIA AND SPINAL ANESTHESIA 557 ondly, to select such a spot as will insure the most direct possible entry of the fluid into the circulation about the cord." He reasoned that, if placed between the spinous processes of the vertebrae, "the anesthetic would be rapidly absorbed by the minute ramifications of the veins referred to, and, being carried by the blood to the substance of the cord, would give rise to anesthesia of its sensory and perhaps also of its motor tracts.'^ It was with this conception of the matter that Corning carried out his early, experiments, first upon a dog and then upon a man. In the case of the man, who was suffering from spinal weakness and seminal incontinence, 30 minims of a 3 per cent solution of cocain were injected between the spinous processes of the eleventh and twelfth dorsal vertebrse. These experiments encouraged Corning to proceed with his investi- gations, and in 1888 he published a report ^ of his injection of cocain hydrochlorate in the immediate neighborhood of the cord. The injections were made in the lumbar and dorsal regions, and thus Corning, antedated by three years the work of Quincke ^ with lumbar puncture. Quincke found, independently, being unaware of Coming's work, that it was possible to remove the cerebrospinal fluid after lumbar punc- ture apparently without danger to the subject. He also demonstrat- ed that a considerable amount of the cerebrospinal fluid may be with- drawn. Quincke's experiments were made with a partly different object in view from that which actuated Corning, but the former's discovery un- doubtedly had its effect in stimulating interest in the subject of spinal puncture, as it concerned the induction of spinal analgesia. Following the work of Corning and Quincke, various experiments were made with reference to the effect of medicinal fluids upon the spinal nerves and cord. Ziemssen ^ proposed the injection of such substances through lumbar puncture. Sicard,* in 1898, published the report of a series of experiments in which he injected into the subarachnoid space normal salt solution, ^ Corning : ' ' Further Contribution on Local Medication of the Spinal Cord, with Cases." Med. Bee, March 17, 1888; also ''Headache and Neuralgia," 1888, 157. - Quincke : ' ' Die Lumbalpunktur des Hydrocephalis. ' ' Berl. Min. Woch., 1891, No. 38. ^Ziemssen: Wiesbaden Kongr., 1893. "Sicard: "Essais d 'injections microbiennes, toxiques et therapeutiques, par voie cephalo-rachidienne. " Compt. rend. Soc. de Biol., Paris, April 30, 1898; also ' ' Toxine et antitoxine tetanique par injections sous-arachnoidiennes, ' ' ibid., Nov. 12, 1898. 558 ANESTHESIA tetanus toxin, niorphin, and other substances, and later he reported ^ the results of his investigations concerning the toxic effects of cocain when introduced into the subarachnoid space through the intracranial or spinal route. From his first series of experiments Sicard concluded that the subarachnoid space could receive relatively large quantities of fluid, and that the effects of such fluid injected in this manner varied in propor- tion to the amount of dilution and to the rapidity with which the solu- tion was injected. Independent investigations by Jaboulay ^ confirmed Sicard's conclu- sions. Corning, meanwhile, was still pursuing his experimental studies, and in 1894 he published the details of his method of irrigating the cauda equina with medicinal fluids.^ While he was engaged in testing his method of medicating the spinal cord. Corning became impressed with the desirability of introducing the remedies directly into the spinal canal, "with a view to producing still more powerful impressions upon the cord, and more especially upon its lower segment." "There can be no doubt," he states, "especially if the injection be made between the second and third lumbar vertebrae, that the functions of the lower segments of the cord itself may be powerfully affected in this manner. We have only to conceive of the cerebrospinal fluid being at this point thoroughly impregnated with the medicinal fluid and lying in direct contact with the pia ... to be convinced of the potency of such a procedure." The dangers involved in such an operation were made a matter of consideration by Corning, and his own observations were in accord with the work of Mitchell * and Thoburn.^ Mitchell showed that a simple puncture of a nerve of an animal with a sharp needle causes little bleeding, which passes away without grave results. Thoburn called attention to the harmlessness of such slight trauma- tism as the pricking of the cauda equina. This work was later verified by Crile's investigations.^ He found, ^Sicard: "Inoculations sous-arachnoidiennes chez le chien; voie cranienne, voie rachidienne, ' ' Compt. rend. Soc. de Biol., Paris, Oct. 29, 1898 ; also ' ' In- jection sous-arachnoidienne de cocaine chez le chien," ibid., May 20, 1899. ^Jaboulay. "Drainage de I'espace sous-arachnoidienne et injection de liquides medicamenteux dans les meninges, ' ' Lyon med., May 15, 1898. 'Corning: "Pain," 1894, 247 et seq. ■'Mitchell, S. Weir: "Injuries of Nerves and Their Consequences," 1872. "Thoburn, William: "Injuries of the Cauda Equina," Brain, 10, 381 et seq. ' Crile : ' ' An Experimental and Clinical Kesearch into Certain Problems Ee- lating to Surgical Operations," 1901, SPINAL ANALGESIA AND SPINAL ANESTHESIA 559 from a series of recovery experiments, that it was difficult to locate the point of injection, and that it was only in cases where no aseptic pre- caution's had been taken at the time of the injection that the track of the needle could be traced by the unaided eye, careful inspection failing to reveal the point of injection in cases where such precautions had been taken. Corning ^ emphasized the fact that serious disturbances of sensation and mobility, having their origin in the cauda equina, are always due to gross lesions, and not to insignificant circumscribed causes. Application of the Analgesic Effects of Cocain Upon the Cord to Surgical Operations Below the Diaphragm. — The studies of Corning seem to have made little or no impression upon the minds of the various investigators to whose experiments reference has been made. Despite the fact that he had suggested, in his original contribution, the surgical application of the method,^ no such application had been made until Bier, of Kiel, demonstrated its entire feasibility and published the re- sults of his work.^ Odier,* who injected cocain into the spinal cord of rabbits, noting the resulting protoplasmic changes in the nerve cells and the analgesia of the body below the point of the injection, failed to make any clinical application of the latter finding. With the publication of Bier's paper the surgical application of spinal analgesia was definitely estaljlished. Bier observed the effects of analgesia induced by this method upon himself, his assistants, and six patients. Lumbar puncture, after the method of Quincke, was employed. The passage of the needle was ren- dered painless by means of Schleich's infiltration. He used two cubic centimeters of a one per cent solution of cocain. The appearance of Bier's paper led to the immediate adoption of the method by many surgeons throughout the civilized world, but especially in France and America. His findings were verified by Seldowitch,^ experimenting upon dogs. Tait and Caglieri ^ are credited with having performed the first sur- * Corning: "Pain," 1894. ^Corning: Oy. cit. (N. Y. Med. J., Sept. 19, 1885)— "Whether the method will ever find an application as a substitute for etherization in genitourinary or other branches of surgery, further experience alone can show." * Bier : ' ' Versuche iiber Cocainisirung des Eiickenmarkes, ' ' Deut. Zeit. f. Chir., Leipzig, 1899, 361. * Odier : ' * Eeeherches exp^rimentales sur les mouvements de la cellule ner- veuse de la moelle epiniere, ' ' Eev. Med. de I. Suisse Romande, 1898, IS, 59. * Seldowitch : ' ' Ueber Cocainisirung des Eiickenmarkes nach Bier, ' ' Ceniralbl. f. Chir., 1899, 41, 1110. * Tait and Caglieri: "Experimental and Clinical Notes on the Subarach- noid Space," Trans. Med. Soc. State of Cal, April, 1900, 266. Also, /. Am. Med. Assn., July 7, 1900. 560 ANESTHESIA gical operation under spinal analgesia in America, on October 26, 1899. Osteectomy of the tibia, in a patient fifty-four years of age, was per- formed without pain or discomfort, and with no unpleasant after-effects. One c. c. of a % per cent solution of cocain was employed. The procedure was "popularized" by Tuffier,^ who extended the appli- cation of the method from its original domain of the lower extremities, as practiced by Bier, to the genito-urinary organs and abdomen. He subsequently performed hysterectomy, salpingectomy, nephrectomy, pylorectomy, cholecystectomy, etc., under subarachnoid analgesia. The position of spinal analgesia in the surgical world was established upon a firm basis by the work of Bier, Tait and Caglieri, Tuffier, and others of the early investigators, and the literature of the subject at once began to assume extensive proportions. The scope of the applica- tion of the procedure was quickly extended, and the method came to be employed in old and young, for divers conditions, and with varying de- grees of skill and success. It was not long until Bier felt called upon to protest ^ against the recklessness with which the method was being employed, regardless of the fact that no noteworthy improvement in technique had been evolved. He protested especially against the dangerously large doses of cocain which some operators used. New methods, he said, should be devised in an attempt to reduce the toxicity of the drug and to prevent the un- pleasant by-efi^ects so often noted. He suggested the application of the procedure to operations upon the entire trunk and arms, and made a plea for an effort to find less harmful drugs which would produce anal- gesia by this method. In obstetrical practice subarachnoid analgesia was employed early in its history, Kreis ^ being credited with having first made this application of the method. Doleris,* Marx,^ Dupaigne,*^ and others utilized the pro- ^ Tuffier: (1) "Analgesie chirurgicale par I'iiijection sous-arachnoidienne lombaire de cocaine," Soc. de Biol., Nov. 11, 1899, in Semaine med., 1899, 389; also, La Presse nled., Nov. 15, 1899, 294; (2) "L'Analgesie chirurgicale par voie rachidienne, " 1900. In L'CEuvre me dico-chirur gical, Critzman, 1901-02, 24-30. ^ Bier : ' ' Bemerkungen zur Cocainisirung des Eiickenmarkes, ' ' Miinch. med. Woch., Sept. 4, 1900, 1226. 'Kreis: "Ueber Medullarnarkose bei Gebarenden, " CentrlM. f. Gyn., July 14, 1900, 724. *Doleris: "Analgesie par injection de cocaine dans I'arachnoide lom- baire," Compt. rend. d. I. Soc. d'Obst., de Gyn., et d. Pediat. d. Paris, 1900, S, 328. °Marx: (1) "Medullary Narcosis During Labor, a Preliminary Eeport, " Med. News., Aug. 25, 1900, 293; (2) "Medullary Narcosis During Labor," Med. Bee, Oct. 6, 1900, 521; (3) "Analgesia in Obstetrics Produced by Medullary Injections of Cocain," PMla. Med. J., Nov. 3, 1900, 857. "Dupaigne: "Anesthesie rachidienne par le cocaine," Ann. de Gyn. et Obst., Paris, 1901, 55, 44. SPINAL ANALGESIA AND SPINAL ANESTHESIA 561 cedure for the same purpose. My own experience with spinal analgesia in obstetrical practice is limited to one case, but this was an excellent one in which to test the method in this class of cases. (See case descrip- tion on page 593.) In the early stage of the surgical application of spinal analgesia the author of this section began to employ the method, being particularly interested at that time in its use in young children. >Seven cases oper- ated upon under spinal analgesia were reported,^ the youngest being 21/^ and the oldest 11 years of age. The former case was apparently the youngest in which the method had been employed at that time. The youngest cases on record at that time were: One, 8 years, operated by Murphy; one each at 11 years, by Bier, Lugueu, and Kinder jy, and one, 12 years, by Tuffier. An additional series of forty cases ^ was reported during the follow- ing year, the youngest of this series being 7%, and the oldest 19 years of age. Twenty-four of these cases were reported in detail. Eeport ^ was published of twelve operations upon infants and young children ranging in age from 3 months to 5 years. Of this series the history of that case. No. XII, is detailed on page 588. Tuffier ■^ reported a case in an infant 3 months old. Extension of the Surgical Application of Spinal Analgesia to Parts of the Body Above the Diaphragm. Experimentation with Other Agents. — It is impossible, within the limited space, to follow the work of the very large number of surgeons who have devoted attention to the subject of spinal analgesia during the years which have intervened since the appearance of Bier's original communication.^ The historical con- tributions, other than those mentioned, have been largely in the nature of modifications of technique, and the verification of the earlier results by a large number of clinical cases. With certain notable exceptions, both the experimental and the clini- cal investigations were concerned with the production of analgesia below the diaphragm and its application to the surgery of those regions. Tait and Caglieri," in 1900, reported 3 cases in which cocain was injected into the sixth cervical space without untoward effects. The ^ Bainbridge : "Analgesia in Children by Spinal Injection, witli a Eeport of a New Method of Sterilization of the Injection Fluid," Med. Bee, Dec. 15, 1900. ^Bainbridge: "A Eeport of Twenty-four Operations Performed During Spinal Analgesia," Med. News, May 4, 1901. 'Bainbridge: "Eeport of Twelve Operations on Infants and Young Children During Spinal Analgesia, ' ' Archives of Pediat., July, 1901. ^Tuffier: "Sur la rachicocainisation, " La Presse med., Paris, June 8, 1901, 265. = Bier: Op. cit., Pent. Zeii. f. CUr., Leipzig, 1899, 51, 361. ''Tait and Caglieri: Op. cit.. Trans. Med. Soc. State Cal., April, 1900, 266. 562 ANESTHESIA patients were examined weeks after the injection and found to be free from any complication. Morton/ in 1900, also presaged the recent extension of spinal anal- gesia to surgicai operations upon all parts of the body. "I think," he said, "we will soon find that, by injecting higher into the dorsal region, anesthesia can be extended all over the body with perfect safety. It has been demonstrated in the dog by making an injection in the upper part of the dorsal region. It does not interfere with motion, consciousness, or sense of touch." In a later communication ^ Morton said : "I think we have a safe and reliable analgesic in the subarachnoid injection of cocain for the performance of any surgical operation on any portion of the body, re- gardless of age, sex^ or disease, and one which has no contraindications." In this report Morton tabulated 253 cases operated upon by him, 24 in females, 229 in males, 8 of the operations being above the diaphragm. An additional series of 61 cases was added to the above report, 15 of which were upon the upper extremities or head. The analgesia was com- plete in all cases. One case in which the operation was above the dia- phragm was reported in detail.^ Chaput and others performed operations on parts of the body above the diaphragm under spinal analgesia. It appears that the work of Tait and Caglieri, Morton, and others, with high injection, has not been followed up with further published clinical application, for which reason, perhaps, originality in this regard has been generally accorded to Jonnesco. In September, 1908, before the Congress of the International Society of Surgery, in Brussels, Jonnesco,* of Bucharest, described his new method of general spinal anesthesia, and reported 14 cases operated upon by this method. The method is detailed, and selected cases cited, 103 of which were high dorsal analgesias, and 295 dorso-lumbar anal- gesias. In a later article ^ Jonnesco says : "It is an error to confuse lumbar rachianesthesia, conceived by Corning and popularized by Bier, with my method. As I have many times emphasized, my method is a new one and altogether distinctive, because I have generalized spinal anesthesia, adapting it to all operations on any part of the body. This has not yet ^Morton: "Is the Subarachnoidean Injection of Cocain the Preferable Anes- thesia Below the Diaphragm?" Pac. Med. J., Nov., 1900. 2 Morton: "The Subarachnoid Injection of Cocain for Operations on All Parts of the Body," Am. Med., Aug. 3, 1901. ^ Morton : ' ' Eeport of a Lipoma Eemoved from the Cheek under Medullary Narcosis," FMla. Med. J., July 6, 1901. ■'Jonnesco: "Eemarks on General Analgesia," Brit. Med. J., Nov. 13, 1909. ^Jonnesco: "Concerning General Eachianesthesia, " Am. J. of Surg., 1910, g9. 33. SPINAL ANALGESIA , AND SPINAL ANESTHESIA 563 been done by others, although it is now a year and a half since I read a paper on this subject at the International Surgical Congress in Brussels. I secured this anesthesia by piercing the spinal column at all levels, and by adding strychnin to the anesthetic stovain, novocain, tropococain, etc." Jonnesco holds that the fact that the respiratory nerves are not in- volved in the high injections, although all the other nerves of that spinal region, are paralyzed, is due to the influence of the strychnin. To this latter statement reference will be made under the head of physiological action. In the addition of the strychnin to the analgesic solution Jonnesco is evidently original. As early as 1903, however, the author of this sec- tion used strychnin hypodermatically in conjunction with spinal anal- gesia, with the same ends in view, of supporting the jDatient and pre- venting respiratory depression. Following the suggestion of Bier concerning the desirability of dis- covering some more suitable drug than cocain for spinal analgesia (see page 560), a large amount of experimental work has been done with a view to accomplishing this end. Tropacocain, stovain, novocain, beta-eucain, beta-eucain lactate, alypin, nirvanin, holocain hydrochlorid, acoin, orthoform (new), and anesthesine are some of the drugs which from time to time have been made the subject of experimental or clinical investigation. (See page 599.) A full list of all substances which have been prepared is given in Chapter XX. ANATOMICAL AND PHYSIOLOGICAL CONSIDERATIONS With the discovery by Cotugno (Dominicus Cotunnius), in 1764, of the "collection of water about the brain and in the spine," a new interest was given to the cerebrospinal column. The observations of Cotugno upon the bodies of animals were confirmed by him upon human sub- jects, and his declaration that the nervous centers were bathed by this cephalo-spinal fluid called forth a brief but very good description by Haller, in 1766, and a complete study by Magendie, in 1825, Follow- ing these early investigators, a number of others continiied the study of the anatomy and physiology of the cerebros^^inal canal. Coming's experiments with reference to the local medication of the cord, and the discovery by Quincke that it is possible to remove the cerebrospinal fluid by lumbar puncture without danger to the subject, gave a still more definite interest to this region. The surgical application, made by Bier, of the discoveries of Corning and Quincke called forth an extensive series of investigations concerning the anatomical and physiological rela- tions of the vertebral canal. 564 ANESTHESIA The extent of the experimental and clinical study devoted to this subject may be imagined when one realizes, as stated by Mott/ that in the ten years preceding 1910 there appeared in the Revue Neurologique abstracts of 187 papers on the physiology of the cerebrospinal fluid. Despite the many contributions to the subject, there is a notable diversity of opinion with reference to certain practical points relating to the physiology of the cerebrospinal canal and its contents, as will be seen. Among the more recent investigators of the anatomical relations of the canal, Gerstcnberg and Hein " and Lusk ^ have given valuable practi- cal contributions. Michelson * and others have emphasized the impor- tance of bearing in mind that the spinal fluid bathes a number of cranial nerves, as well as the spinal roots, so that those nerves may also become exposed to the toxic action of the analgesic agent when it passes to a sufficient height in the clural sac. The abducens, troclihar, motoroculi, and optic are the cranial nerves primarily, and most frequently, involved in spinal analgesia. It is to be taken for granted that the general anatomy of the parts involved is a matter of accurate knowledge on the part of the surgeon who undertakes spinal puncture, for which reason no space is given to this subject. Certain practical points which are directly concerned in the matter of the selection of the site for puncture, and in controversy relating to lateral or median puncture, are reserved for the section on Sites of Injection. (See p. 605.) Physiological investigation has established certain facts with refer- ence to the cerebrospinal fluid which have a practical bearing upon spinal puncture and spinal analgesia. The composition, origin, density, volume, pressure, drainage, and motion of the fluid have been made the subject of exhaustive research, formerly by physiologists and neurolo- gists, and latterly by those especially interested in its utilization for therapeutic purposes, particularly with reference to spinal analgesia. Origin. — Faivre, in 1851, suggested the intimate relationship between the choroid plexus of the central nervous system and the cerebrospinal fluid. Subsequent investigation has tended to support the view that the cerebrospinal fluid is a secretory product of the epithelial cells of the choroid plexus and of the ependyma membrane. ^Mott, F. W.: "The Cerebro-spinal Fluid," Lancet, July 2 and 9, pp. 1 and 79, 1910. ^ Gerstenberg and Hein : ' ' Anatomische Beitrage zur Riickenmarkesanasthesia, ' ' Z. f. Gehurtsch. u. Gyn., 1907-08, 61, .524; also, Verhandlungen der GesellscJiaft f. Geburtsh. u. Gyn., zu Berlin, 1907-08. 'Lusk, William C. : "The Anatomy of Spinal Puncture with Some Con- siderations on Technic and Paralytic Sequels," Ann. of Surg., Oct., 1911, 449. * Michelson: "Der gegenwartige Stand der Lumbal-anaesthesie, " Ergebnisse der Chir. und Ortho., 1912, 4. SPINAL ANALGESIA AND SPINAL ANESTHESIA 565 Volume. — There is abundant evidence of the fact that the cerebro- spinal fluid is continually being secreted. The quantity in the subarach- noid space, the ventricles of the brain, and the central canal of the spinal cord is said to vary from 50 to 150 c. c, the average being from 100 to 130 c. c. (See pp. 619 and G24 Dry Spine.) Specific Gravity. — According to Gray, who studied the cerebro- spinal fluid in a series of normal children, from whom it was obtained on the operating table, the specific gravity varied from 1.0054 to 1.0071. In cases of extreme shock the specific gravity rose to 1.0076, 1.0080, and 1.0083. The fluid of older children tended to be of a higher density than that of infants and younger children. The specific gravity of the fluid in adults is stated by ISTogue - to vary from, an average of 1.003 to as high as 1.020. By the majority of the writers consulted it is stated to vary from 1.004 to 1.007. Movements. — The cerebrospinal fluid is in constant motion. Being constantly secreted, it is likewise continuously drained through the arachnoid sheaths of the nerves, the perivascular lymphatic sheaths, and, according to some observers, the "Pacchionian bodies. This subject has been studied by Schwalbe, Key and Eetzius, Tait and Caglieri, Klose and Vogt, and a number of others, and recently reviewed by Chambard." When sepia, India ink, or other colored fluid is injected into the canal, the colored corpuscles accumulate around the nerve roots and the cranial nerves near their exit orifices. The elimination in this manner of soluble substances injected into the fluid illustrates the meningeal per- meability from within outward. In addition to the constant drainage of the cerebrospinal fluid there are also pulsation, a systolic flux and reflux, and a transportation, under certain circumstances, of the entire bulk of the fluid, as when, in tlic horizontal position, the fluid is transported on to the medulla and the brain. Pressure. — -The pressure under which the fluid exists is dependent upon the cerebral circulation, and varies under certain circumstances and in different positions of the body. The actual pressure is taken by lum- bar puncture in the sitting posture. This has been found by Quincke to vary from 50 to 150 millimeters of water. Diffusion. — Tait and Caglieri,* in their valuable experimental and clinical work on the subarachnoid space, employed a large number of ^ Gray, H. Tyrrell : "A Study of Spinal Angesttesia in Children and In- fants," Lancet, Sept. 25 and Oct. 2, 1909. ^Nogue: " Anesthesie, " Traite de StomatoJogie, 1912, 6, Paris. 'Chambard: " L 'Anesthesie Lombaire, " These de Paris, 1911. *Tait and Caglieri: Op. cit., Trans. Med. Soc. State of CaJ., April, 1900, 266. See, also, /. Am. Med. Assn., July 7, 1900. 566 ANESTHESIA animals and a series of cadavers, and several patients were subjected by them to lumbar puncture for therapeutic purj)oseG, Avith the hope of clearing up certain doubtful points relating to the physiology of the subarachnoid space. By means of their experimental work on animals and their clinical studies on man, these investigators confirmed the theory that absorption and elimination occur when chemical substances are injected directly into the subarachnoid space, and that the osmotic current exists in only one direction; in other words, as shown by Sicard, that there is exos- mosis, but no endosmosis. The mode of diffusion of the cerebrospinal fluid was studied by means of colored mixtures, which enabled the workers to note with ac- curacy and facility both the miscroscopic and the macroscopic results. When injected without pressure, the colored fluid stained the space at the point of injection, then diffused in all directions, ascending and de- scending, following the meningeal prolongations along the spinal nerves, to the intervertebral foramina, where it stopped abruptly. The extent and the rapidity of the diffusion were influenced by the amount, the composition, and the specific gravity of the liquid injected, and chiefly by the pressure under which it was injected. It was foimd that a slow injection of 1 c. c. of the colored mixture, in a rabbit weighing 900 gm., ascended rapidly, the fluid being found around the medulla oblongata and at the base of the brain when the animal was killed 10 hours after the injection. The same amount of fluid injected under pressure was found 2G hours later to have diffused from the spinal subarachnoid through the foramen of Magendie to the fourth ventricle, through the iter a teriio, or aqueduct of Sylvius, to the third ventricle, and finally to the cortex of the brain. If 5 c. c. of the colored fluid were injected under great ■pressure in the lumbar space, the diffusion occurred instantaneously. Experiments were instituted to determine the course followed by the fluid from the lumbar space to the cortex of the brain. It was found that the pia-arachnoid was colored in its entire course along the cord and brain, continuing along the sheath of the auditory, facial, and optic nerves, and following the prolongations through the cribriform plate of the ethmoid. The stain followed the meningeal sheath on the optic nerve, generally stopping at the junction with the sclerotic. In several of their specimens Tait and Caglieri found that the stain in- volved the sclerotic, choroid, papilla, and retina. Halbreich,^ from a series of experiments on dogs and frogs, con- cluded that the solution, when injected in the lumbar region, is the more liable to reach the medulla oblongata the larger the quantity of fluid injected and the more the head of the subject is lowered. The 'Halbreich: Med. Oios., Eussia. Abst. in J. Am. Med. Assn., 1902, 603. SPINAL ANALGESIA AND SPINAL ANESTHESIA 567 gray matter is penetrated, according to this investigator, by diffusion and osmosis, and by the lymphatics. Crile,^ in his studies upon the cord, injected a solution of cocain, which was colored with methylene blue. He found that an injection of V^ dram of this solution, made in the lumbar region, stained the entire cord and the under surface of the brain in 30 seconds. The various localized functions of the cord and medulla were rapidly anesthetized, the respiratory center in the medulla, for example, being anesthetized within a few seconds l)y lumbar arachnoid injection. A forcible injec- tion was followed within a few seconds by a direct fall in blood pressure and by cessation of respiration. Crile found that the fluid ascended about as rapidly with the subject in a vertical position as in the hori- zontal, and he concluded that the effect of the anesthetic was due to local contact with the nerve structure, and not to absorption. This view, he held, is in full accord vv^ith the general action of cocain on other nerve structure. Crile purposely employed large doses in these experi- ments in order to determine the control, or, as he expresses it, the want of control, the operator can have over the extent of the analgesia. The attempt to ascertain to just what physiological action of the analgesic agent the analgesic state may be attributed in the case of subarachnoid injection has led to various theories of more or less con- tradictory character. Bier ^ held that the sequence of symptoms following the injection is the result of changes in the circulation caused by the introduction of a heterogeneous substance into the spinal canal, and that it is not due to any toxic action of the cocain. Nicoletti ^ attributed it to the vasomotor constrictive action of the injected agent. Goldan * held that the circulation is no factor in the production of analgesia when cocain is injected into the subarachnoid space, the effects being due, in all probability, to the passage of the cocai-n from the subarachnoid space along the perivascular spaces in the tunica adven- titia of the blood vessels to the sensory columns of the cord, also directly into the lymph spaces of the nerves themselves. The investigations of Donitz and Barker seem to have led to different conclusions with respect to the manner of extension of the analgesia. ^ Crile,. George W. : "An Experimental and Clinical Eesearch into Certain Problems Relating to Surgical Operations." Phila., 1901, 145 et seq. ^Bier: "Bemerkungen zur Cocainisirung der Riickenmarkes, " Miinch. med. Woch., Sept. 4, 1900. ^ Nicoletti : " L 'analgesia cocainica del midollo spinale nella chirurgia gine- cologica, " Treizieme Congres International de Med., Paris, Sec. de Chir. Gen., 1900; see, also, Archiv. Hal. di Ginicol., Aug. 1900, 512. * Goldan: "Intraspinal Cocainization for Surgical Anesthesia," Med. News, Nov. 3, 1900. 568 ANESTHESIA Donitz ^ maintains that it is not a question of diffusion, but simply one of shifting the balance in the liquor spinalis, which takes place at the moment of the change of posture; that "it is not a question of the action of . gravity on the analgesic compound at all, nor is it one of hypothetic currents." Barker,^ on the other hand, in his interesting series of clinical ex- periments, makes use of gravity by employing an injection compound of much greater specific weight than that of the liquor spinalis. As- suming that there are only three ways in which an analgesic fluid in- jected in the second lumbar interspace can make its direct effects felt in the mid-dorsal region or higher. Barker says with reference to these, in sequence: "(1) Diffusion alone of one fluid in another is a slow process, and, as we shall see, is unlikely to be the mode of spread of the injected fluid in this procedure. "(2) Bier and his followers have aimed at shifting the whole in- jected compound upward or downward with the whole mass of the liquor spinalis by raising or depressing the pelvis. That the cerebrospinal fluid does recede somewhat toward the head on elevation of the pelvis is undoubted, but it is hard to imagine its doing so to such an extent as to carry with it a cloud of fluid lighter than itself from the second lum- bar to the fifth dorsal vertebra, some 8 to 10 inches. I venture to think that with such a fluid as he has used, whose specific gravity is 1.0058, suspended in the liquor spinalis, whose specific gravity is 1.0070, what he has achieved by elevation of the pelvis has rather been a more rapid diffusion of the injected drug, due to the consequent oscillation of the spinal fluid, aided, perhaps, by vascular pulsation. But this rapid diffu- sion would, of course, dilute the injection, and perhaps carry it further than desirable. "(3) There remains, then, the third possibility, namely, that an injected compound heavier than the liquor spinalis may be affected by gravity, and sink through the latter in a way quite different to the be- havior of a fluid of less specific gravity, such as that referred to." Other investigators, notably Babcock,^ by using an injection fluid lighter than the cerebrospinal fluid, seek to affect the sensory nerves without involving the motor nerves. The regulation of the position of the patient's body, with such a fluid, controls the area affected by the ^ Donitz : ' ' Die Hohenausdeliung der spinal Analgesic, ' ' Munch, med. Woeh., Nov. 27, 1906. ^ Barker : "A Report on Clinical Experiences with Spinal Analgesia, ' ' Brit. Med. J., March 23, 1907. ^Babcock, W. Wayne: (1) "Spinal Anesthesia. A Clinical Study of 658 Administrations," Fenn. Univ. Med. J., Aug., 1909; (2) "The Eange of Activity and the Untoward Effects of Certain Spinal Analgesics; Based on Two Thousand Administrations," Trans. Am. Ther. Soc, 1910, 57. SPINAL ANALGESIA AND SPINAL ANESTHESIA 569 analgesia. The rate of diffusion of the lighter fluid is controlled by the addition of a larger or smaller percentage of alcohol. Babcock holds that the analgesic drug is decomposed by the cerebrospinal fluid, which still further limits its field of activity. The less the alcohol used, the more rapid, is this decomposition; hence, as the fluid diffuses, it decomposes, and the anesthetic effect can be limited very largely to any desired por- tion of the spinal canal. Tufiier,^ considered the analgesic action of the agent to be local, whether it be exerted upon the cord, the nerve roots, or the spinal ganglion, being not determined. He inclined to the belief, however, that it is confined exclusively to the nerve roots. The early symptoms, such as malaise and trembling, he attributed to the direct action of the anesthetic agent upon the spinal axis. Spiller and Leopold ^ experimented with stovain in an effort to de- termine certain points with reference to the action of this agent upon the nervous system. They thought that perhaps stovain, which produces temporary anesthesia, might, by repeated injections, produce anesthesia of gradually increasing duration until a finally persisting loss of sensa- tion, resulting from organic change, might ensue. They desired to ascertain whether a systemic degeneration of the posterior roots and their continuation in the posterior columns of the cord is the common result of the repeated use of stovain. They also desired to determine whether the paralysis that occurs in stovain anesthesia is of a motor or sensory type, i. e., whether it is produced by changes in the peripheral motor neurons, or is the result of ablation of all afferent impulses which normally pass over the posterior roots. They called attention to the fact that reflex action and all recognition of toxicity of the limbs, and neces- sarily of the position of the limbs, are lost if all peripheral afferent im- pulses are cut off. In order to satisfy themselves upon these points with reference to stovain, Spiller and Leopold experimented upon dogs, 5 subjects being employed. They performed lumbar puncture, using stovain in doses of 0.05 gm. to 2 gm., the injections being usually at intervals of 2 or 3 days. They divided the symptoms into temporary and permanent. The temporary symptoms consisted of flaccid paralysis and complete or par- tial sensory loss. The permanent symptoms consisted of ataxia, de- creased sensation, and, in one case, loss of patellar reflex. The symp- toms became permanent after the third injection, remaining until the end of the experiment. These investigators considered that their experiments clearly demon- strated that stovain affects especially the anterior and posterior roots of ^Tuffier: Op. cit., La Presse medicale, June 8, 1901. * Spiller and Leopold : ' ' The Effects of Stovain on the jSTervous System, ' ' /. Am. Med. Assn., June 4, 1910, 1840. 570 ANESTHESIA the cord. The degeneration of the posterior root fibers was intense, as was likewise that of the intramedullary portion of the lumbar and sacral posterior root fibers in the thoracic region. The posterior thoracic roots were unaifected. Stovain evidently causes slight degeneration in the periphery of the anterolateral columnS;, but has less effect here than on the nerve roots. The lesions obtained by them could not have been produced, they hold, by the trauma of the needle, as the sections of the lumbar region examined were i/^ to 2 inches above the point of injection, and yet the posterior and anterior roots were greatly degenerated. 'Tt would be unwarranted," they conclude, "to apply these findings too strictly to man, as no grave changes have been found as yet in the human cord. At most, our findings would shov/ that repeated injec- tions of stovain might be injurious, and would make one cautious in em- ploying several injections within a short time in the same subject." Spielmeyer ^ examined human spinal cords in his study of the pathc logico-anatomical considerations involved in spinal analgesia. He ex- amined the central nervous system of 13 patients who had died from various causes within from 2 to 8 days after spinal analgesia with sto- vain. In all except 1 case death was in no way related to the spinal analgesia. In 1 case death was due to respiratory paralysis 40 hours ^fter the operation. Upon examination of the woman who died from respiratory paraly- sis advanced changes in the cells of the spinal cord were found. Spiel- meyer did not regard these as a direct effect of the analgesic agent, simi- lar changes having been found in other cases in which death was due to respiratory paralysis of different origin. In three other cases Spiel- meyer was enabled to demonstrate characteristic changes in the polygonal motor cells of the cord. The cells of the posterior horn and the spinal ganglia presented no changes. Spielmeyer was able to pro- duce, experimentally, similar changes in the motor ganglion cells of dogs and monkeys. Michelsson holds the view that, as this histological picture exactly corresponds to the phenomena which usually follow upon the destruction of the axis cylinder, it must be left undecided whether a primary or secondary effect of stovain upon the ganglia is responsible, although animal experiments rather favor the first assumption. It is certainly remarkable, he says, that these changes can be observed only on the mo- tor ganglion cells, high up in the cervical cord, and that there is always a predominating num.ber of normal polygonal cells, besides the affected cells. This probably accounts for the fact that motor disturbances were ^ Spielmeyer : ' ' Pseudosystemer-krankungen des Eiiekeimiarkes nach sto- vainanasthesie, " Neurol. Centrlbl, Jan. 16, 1909, 69; see, also, Miinch. med. Woch., Aug. 4, 1908, 1629. SPINAL ANALGESIA AND SPINAL ANESTHESIA 571 not noted in any of Spielmeyer's cases in man or in animals. In the 13 cases Spielmeyer employed stovain in doses of 0.12 gm. Patients who had received the customary dose of 0.05 gm. to 0.07 gm. presented no changes in the central nervous system, so that the assumption would seem to be justified that this stovain dose as a rule does not produce any lesions of the ganglion cells. Klose and Vogt ^ employed tropococain and novocain in a series of experiments, which led them to the same results as those obtained by Spielmeyer with stovain. These investigators found that the injected agents are distributed over the entire space occupied by the cerebrospinal fluid within half an hour at the latest. The specific gravity of the solution, and the posi- tion of the animal, are of subordinate importance. The alkaloids re- main for a disproportionately long time in the cerebrospinal fluid. Among the agents examined by them, tropococain persisted for relatively the shortest time, stovain for the longest, novocain ranking midway between. In this scale of excretion the duration of the absorption, the so- journ in the blood, and the duration of the analgesia stand in direct proportion to the time after which absorption begins. Following the work of Klose and Vogt, Barker ^ conducted a series of experiments to determine how long stovain remains in the dural sac after injection, unabsorbed, fixed, or destroyed; what effects, apart from analgesia, the agent produces; what immediate and remote effects, if any, the drug has upon the structures with which it comes in contact; and how the agent is eliminated from the system generally. Attention is directed by him to the importance of determining these points with reference to the various analgesic compounds or agents before this method of inducing analgesia can be put in its proper place among sur- gical procedures. In nine of his cases previously injected with stovain Barker with- drew the cerebrospinal fluid, for various reasons, at periods varying from half an hour to forty-six hours after injection. Stovain was found to be present in six cases, the time after injection ranging from one-half hour to twenty-four hours; negative in one case at forty-four hours; and doubtful in two at forty-five and forty-six hours respectively. The question whether any immediate effect is produced upon the structures within the dura by the stovain injection was answered, in Barker's experience, in the affirmative. In all the cases in which he withdrew cerebrospinal fluid within 46 hours of the injection of stovain ^ Klose and Vogt : ' ' Physiologisclie imd anatomische Untersuchungen zur Lumbalanasthesie und zur Frage ihrer klinischen Verwertharkeit, " Miinch. med. Woch., March 9, 1909. - Barker : ' * Elimination of Stovain After Spinal Analgesia, ' ' Brit. Med. J., Sept. 18, 1909, 789. 572 ANESTHESIA into it the fluid was distinctly turbid. The turbidity was found on microscopical examination to be due to the presence of leukocytes of various forms. The theory that the headache which sometimes follows spinal analgesia is due to aseptic irritation and hypersecretion within the dura did not seem to Barker quite satisfactory. Barker fouiid from the study of his cases that, long after the anal- gesic effect of the drug has passed off, stovain or its base can be shown to be unmistakably present in the cerebrospinal fluid. No satisfactory answer could be given to the question, Why does the analgesia last for only a couple of hours? He suggested that only perfect stovain is analgesic, and that its base split off by the alkaline cerebrospinal fluid is not, and that this base is what is recovered in subsequent tappings. From his clinical studies he thought it clear that no permanent structural change in the nervous structures leading to definite symp- toms has been proved to be due to the injections. From the foregoing references to the experimental work of various investigators it will be noted that the physiological action of cocain and other analgesic agents when injected into the subarachnoid space was not clearly understood in the earlier stages of the development of spinal analgesia, and that the studies of later investigators have not served to fully settle these problems. COURSE, EXTENT, AND DURATION OF ANALGESIA Course. — The course of the analgesia, or the sequence in which the various parts of the body are affected, varies with the individual, the point of injection, the agent employed, and the technique. As a rule, in lumbar analgesia, after a minute or so, sensibility to pain is lessened in the perineum, external genital organs, and the inner side of the thigh. The first reflex to disappear is the patellar, which is quickly followed by the disappearance of ankle clonus. Loss of sensi- bility to pain follows, in the order named, in the posterior surface of the thighs and legs, the soles of the feet, and the anterior surface of the legs, and the thighs up to Poupart's ligament. The analgesia then gradually extends to the umbilical region, and from that zone on, in some instances, higher and higher, until universal analgesia, as this may be determined from superficial tests, supervenes. In some in- stances this includes the mucous membranes of the mouth, nose, and larynx. The course of the disappearance of sensibility to pain is segmental, proceeding from the fourth or fifth sacral, segment by segment, to what- ever limit it reaches in the individual case. Extent. — Analgesia may be partial or complete, with reference to Fig. 235. — Operation Under Way for Removal of Tumor of Abdominal Wall Under Spinal Analgesia. Ten minutes after puncture. Face screen in position. Fig. 236. — Second Operation, Same Analgesia, Same Patient as in Figure 235. Exsection of varicose veins, both legs; patient reading, resting paper against face screen. 574 ANESTHESIA the extent of the body involved, as well as to the degree to which sensa- tion is abolished. The term complete is generally employed to signify the degree of loss of sensation, particularly pain sense, though the word is not infrequently used with reference to the extension of the analgesia over the entire body. For the latter purpose the word universal is perhaps preferable. When the cerebral cortex becomes involved, the analgesia merges into true anesthesia, during which the patient loses consciousness, or lapses into a deep sleep with snoring. In the majority of instances in which the analgesic agent is injected Fig. 237. — Same Patient as in Figures 235 and 236. At End of Operation. While the wounds are being sutured, She drinks a cup of tea; facial expression shows absence of pain or discomfort. into the lumbar or lower dorsal region the analgesia extends to the um- bilical region. Under different circumstances the height to which this goes varies, as previously noted. It not infrequently happens that complete analgesia to a very high level, or even universal analgesia, follows the introduction of moderate doses of the analgesic agent into the lumbar region. Morton,^ in 1903, published a record of 929 cases operated upon be- low the diaphragm and 76 above it. In one case he removed the entire superior maxilla for carcinoma, the analgesia being complete. He intro- duced in this case half a grain of cocain between the third and fourth lumbar vertebrae. ^Morton: "Excision of the Superior Maxillary Under Medullary Narcosis, " Am. Med., March 21, 1903, 451. SPINAL ANALGESIA AND SPINAL AN1^:STHESIA 575 Chaput ^ noted that in 53 of 102 cases the analgesia exiended ahove the diaphragm, the arms being involved in 31, the face in 13; while in 9 cases the analgesia of the head was complete. 'J'his high analgesia was obtained by the rapid and forcible injection of large doses of cocain. Pedeprade ^ noted 5 cases in which analgesia was complete through- out the body. Tuffier ^ reported the removal of a cyst of the lung under medullary analgesia. In 4 of the writer's early cases the analgesia extended over the entire body, even the mucous membrane of the mouth and larynx being com- FiG. 238.— Enlarged Picture of Patient's Face Showing Facial Expression. pletely analgesic, as recorded m a personal letter to Patterson and in- corporated by the latter in his admirable resume of the literature of spinal analgesia.* In 27 other cases, operated upon under lumbar anal- gesia, with moderate doses, the analgesia was sufficiently extensive to have rendered painless operation upon the upper part of the body. A typical instance of universal analgesia ° was that of a female pa- tient, aged 11^^ years, who was suffering from tuberculous abscesses of the foot, with tarsal necrosis. On February 7, 1901, she was operated upon under cocain spinal analgesia. The injection was made between 1 Chaput : ' ' Sur la Cocaine Lombaire, ' ' Bull, et Mem. d. I. Soc. d. CMr. de Paris, 1901, 883. 2 Pedeprade : "L'Analgesie par injection de cocaine sous 1 'arachiioi'de lom- baire en chirurgie. " Paris, 1901. 3 Tuffier: Op. cit., La Presse med., June 8, 1901. ^Patterson: "Spinal Analgesia. The Present Status of the Method Based on a Review of the Literature," ArcMv Internal, d. CMr., 1, 502; £, 53. ^Bainbridge: "A Report of Twenty-four Operations Performed During Spinal Analgesia," Med. News, May 4, 1901, Case IX. 576 ANESTHESIA the third and fourth lumbar vertebrse, the amount of cocain being 15 minims of a two per cent solution. Analgesia extended to the level of the diaphragm in 2 minutes. The operation lasted 20 minutes, and in- cluded the opening of the abscesses and the removing of carious bone and tuberculous tissue. At the close of the operation, 25 minutes after the injection, there was absolute absence of pain sense over the entire body. Tests proved that the analgesia was present in the conjunctiva, the mouth, on the tongue, and over the posterior pharyngeal wall. A similar instance of complete analgesia occurred in a child five years of age,^ upon whom circumcision was performed. Other cases of anal- gesia extending practically over the entire body are cited. ^ In one case (No. XXII) a tuberculous sinus extending into the external condyle of left humerus was enlarged and dead bone removed. In another (ISTo. XXIV) the left thumb was amputated at the lower third of the meta- carpal bone. In the former case 8 minims of a two per cent solution of cocain were injected between the third and fourth lumbar vertebrse; in the latter 32 minims of a two per cent solution were injected between the second and third lumbar. In a number of recorded instances the analgesia was unilateral, pre- sumably, according to Donitz,^ because the injection was made at the beginning of the eauda equina, in the right or left group of nerve fibers, instead of the cisterna terminalis. Dift'usion is thus incomplete, the so- lution reaching only the contiguous nerve roots, hence producing only partial analgesia, or analgesia of a given side. Duration. — The duration of analgesia induced by subarachnoid in- jection is generally from % of an hour to 1^2 hours, with cocain, sto- vain, and tropococain, the last named being shorter than the other two, and from 21^ to 3 hours, with novocain and adrenalin. Instances have been recorded where the analgesia lasted from 17 minutes to 8 hours. Jonnesco states that with his method analgesia lasts from 1^/2 to 2 hours. The writer has found the analgesia to vary in duration from 45 minutes to 3 hours and 20 minutes. This has reference to the complete return of pain sense. During the early days, when the dosage was so uncertain, when cocain was used exclusively, and when so much was being said concerning the dangers of this agent, very conservative doses were employed, and the analgesia was often of shorter duration than obtains at the present time, when the method is more thoroughly under- stood in all its phases. It may be said, however, that, with all the added knowledge gained from experience, the duration of analgesia is still ' Bainbridge : "Eeport of Twelve Operations on Infants and Young Chil- dren During Spinal Analgesia," Archives of Pediat.. July, 1901, Case I. = Bainbridge: Op. cit., Med. Neivs, May 4, 1901, Cases XV, XXII and XXIV. •JDonitz: Verh. d. deutsch. Gesell. f. Chir., 1905, 536. SPINAL ANALGESIA AND SPINAL ANF^STHESIA 577 problematical, and will doubtless continue to be so until some delinite scientific basis for dosage is formulated. ACCOMPANYING PHENOMENA Subjective. — The manifestation of subjective symptoms begins within from two to eight minutes after the injection is made, varying with different patients. As a rule, the first subjective symptom noted is a tingling sensation and numbness in the feet and sometimerj in the legs. During the first ten minutes or so there is a sense of malaise, charac- terized by a feeling of epigastric heaviness, thirst, and air-hunger. A sensation of cold, or of heat, with sweating, and sometimes salivation, follow the vasomotor reaction to the analgesic agent. In a certain pro- portion of cases there is a trembling of the legs amounting to clonic contractions. There may be cramps in the muscles of the legs. Nausea occurs in about thirty per cent of cases, as culled from the literature by Patterson.^ It seems to bear no relation to the preceding meal. The size of the dose of the analgesic agent injected bears a rela- tion to the nausea, the larger the dose the more certain the nausea. The bulk or volume, rather than the strength, of the injected fluid is held by Gray and others to be the main factor in the production of nausea. Vomiting, which occurs in about forty per cent of cases, begins, as a rule, in from five to ten minutes after the injection, sometimes earlier. It occurs in women more frequently than in men. It is seldom re- peated more than 3 or 4 times. There may be late vomiting, coming on in from 2 to 3 hours after operation, and continuing for 3 or 3 days, according to some writers. Personal experience, and that of all but a few operators, is at variance with this observation. An interesting study of the subjective symptoms has been furnished by Fraicou,- who operated upon himself for hernia under spinal anal- gesia with strychninized stovain. The injection was made by an assistant, between the twelfth dorsal and first lumbar vertebrae, 1 c. c. of water, containing 5 centigrams of stovain and 1 milligram of strychnin, being employed. In addition to this, 2 centigrams of stovain were employed locally in the iliac fossa and external portion of the inguinal region. During the entire operation, which was performed without assist- ance, the analgesia was complete below the anterior superior iliac spines. The body above this level remained unaffected throughout. The anal- ^ Patterson: Op. cit. 2 Fraicou : ' ' Auto-observation d 'une auto-operation de hernie sous la rachi- strychno-stovainizatiou, " La Presse med., Feb. 11, 1911, 105. 578 ANESTHESIA gesia disappeared as the work was drawing to a close, and the suture of the skin was slightly painful. The conclusions formulated from this experience are in part as fol- lows: (1) The pain produced by the spinal puncture is greater than that caused by -a simple subcutaneous injection with the Pravaz syringe. The pain, however, is less disagreeable than the sensations experienced by the majority of patients at the beginning of chloroform anesthesia. (2) The anesthesia became established with pleasant sensations, and disappeared imperceptibly. Fig. 239. — Amputation of Foot Just Above Ankle Joint Under Spinal Analgesia. Operator with clamp grasping sensory nerve and cutting it short; note absence of pain in expression. (3) The mild excitement at the beginning of the anesthesia, and the vertigo which was felt on making sudden movements, are proof of the anesthetic fluid having slightly spread toward the cerebral liemispheres. The intellectual faculties remained absolutely intact, and consciousness was entirely preserved. This is conclusively proven by the fact that the surgeon also conducted a delicate operation upon himself to a successful outcome. (4) The technique of the anesthetic method and the patient's position after the injection are the essential factors on which depend the degree and intensity of the anesthesia. (5) The anesthesia has a great tendency to remain segmental. (6) The harmlessness of the method of rachi-strychno-stovainiza- Fig. 240. — Inguinal Hernia, Inherent Intestine, Adhesions Being Pulled Apart Under Spinal Analgesia. Babcock's diffusible solution. Head lowered. Fig. 241. — Same as Figure 240, Head Elevated. Patient reads to surgeons during operation. 580 ANESTHESIA tion is illustrated by the fact that during the entire anesthesia no un- pleasant incident or phenomenon occurred, aside from vertigo caused by all sudden movements, despite the sitting position which it was necessary, for the operator to maintain throughout. (7) The contrast between the absence of any accident during the anesthesia and the onset of transitory postoperative and postanesthetic symptoms is accounted for by the fashion in which the operation was performed. Although in the upright position, and although the move- FiG. 242. — Same Patient at End of Operation. Patient drinking water. ments during the operation had no influence upon the onset of imme- diate symptoms, they gave rise at least to secondary disturbances. Another instance of auto-observation of the symptoms caused by spinal analgesia was the operation for appendicitis recently performed upon himself by Dr. Bertram F. Alden, chief surgeon to the French Hospital, San Francisco. The following history embraces the auto-observations of a patient operated upon by the author : Miss E. F., 47 years of age, trained nurse. According to her own statement, she had had chronic nephritis for a number of years, with albumin as high as 25 per cent by volume at times, with hyaline, granular and blood casts, crystals of triple phosphate, and kidney and bladder epithelia. This statement was verified by urinalysis previous to operation. For 35 years she had had goiter, which was found to be of the cystic variety. The goiter developed with puberty, since which time SPINAL ANALGESIA AND SPINAL ANESTHESIA 581 she had always been extremely nervous, with more or less functional irregularity of the heart. Eeferred to me, January 5, 1911, })y Dr. E. M. Mosher, of Brooklyn, for multiple uterine fibroids which filled the entire pelvis. On January 11 panhysterectomy and appendectomy were per- formed under spinal analgesia, one-half dram of a 3 per cent solution of stovain being injected between the second and third lumbar vertebrae. The patient's description of her experience follows: "In a few min- utes (5) after the injection the lower extremities became lifeless. Just as the incision was made into the skin of the abdomen my head was raised in order to put a pillow under it. I saw the incision, and felt the doctors working, but experienced absolutely no pain until the last 3 stitches were applied. These caused slight pain. By this time the anal- gesia was gradually disappearing. I slept at short intervals during the operation. I was given during the operation by hypodermic injection 1/100 gr. nitroglycerin and 1/6 gr. morphin, and at intervals small quantities of brandy and water by mouth. After the operation I drank lemonade to the health of the doctors. I was removed to my room per- fectly conscious and free from pain. I had no unjDleasant after-effects from the analgesia. The wound healed by primary union." On February 11, 1911, half of the cystic thyroid gland was removed under local cocain analgesia. Since that time the patient has been per- fectly Avell, resuming her work as a professional nurse. Objective. — Tests elicit the fact that the sense of pain is the first to disappear, while the senses of touch and posture are gradually lost to a greater or less extent, according to dosage. Motor j)areses manifest themselves first in the muscles of the feet, gradually extending upward. The extensors are more pronouncedly involved than are the flexors. From Patterson's ^ investigation of the subject, it appears that in about 30 per cent of the cases there is incontinence of feces, due to the direct insensibility of the rectum. In about 10 per cent of the cases there are urethrovesical symptoms. In all cases the sense of distention, as well as of contact, with reference to the bladder is lost. Pallor of the face and profuse perspiration are sometimes noted. The general observation seems to be that there is a fall of blood pressure following immediately upon the injection, and that this varies with the completeness of the analgesia and "with the parts affected. The pulse rate varies from 80 to 129 beats per minute, but the cardiac rhythm is regular. Babcock ^ holds that surgical shock is less apt to occur with spinal analgesia than with general anesthesia, because of the blocking off of the nerves of sensation in the former. "The shock of the later stages of ^ Patterson : Op. cit. ^Babcock: "Spinal Anesthesia, a Clinical Study of 658 Administrations," Penn. Med. J., Aug., 1909. 582 ANESTHESIA the operation," he says, "is negatived by the emergence of the spinal centers from the depression of the anesthetic. For this reason, under spinal anesthesia it is not unusual to find the pulse stronger and fuller and the patient in better general condition at the end of an operation than at the beginning." In low analgesia the effect upon the respiration is shown in a greater or less increase in rapidity, while the rhythm is practically unchanged. The greatest danger of so-called high analgesia is paralysis of the mus- cles concerned in respiration. This may vary from slight and temporary respiratory embarrassment to complete and lasting respiratory paralysis. Jonnesco ^ holds that such phenomena as pallor, nausea, and sweating rarely occur when the stovain-strychnin solution recommended by him is used. The face, in such cases, retains its normal aspect; nausea occurs in 2.25 per cent, vomiting in 1.25 per cent, and sweating in 2 per cent. He has noticed fecal incontinence in 4 per cent of cases in cachectic, feeble individuals. The pulse, which is slowed by stovain alone, is usu- ally normal in rapidity and strength when the stovain-strychnin solution is employed. Sometimes, according to Jonnesco, it rises to 80 or 90, but always remains strong. The 5 cases in which he noted temporary stoppage of respiration were cases in which he departed from his usual method in some detail. The addition of the strychnin is claimed by him to obviate this difliculty. POSTOPERATIVE PHENOMENA Alessandri ^ contributes a compilation, from the Neuro-pathological Institute in Eome, of the unfavorable accidents and complications fol- lowing spinal analgesia with stovain injections. The nervous system, according to this observer, which has a great affinity for stovain, presents chromatolysis of the nerve cells, which may affect all parts, inclusive of the bulb. In this way paresis of all descrip- tions may follow. Nausea and vomiting are not uncommon, as the im- mediate result of the effect upon the bulb. Syncope and severe respira- tory disturbance are equally frequent. Among the remote results of stovain analgesia mentioned by Ales- sandri are: Hyperthermia, up to 40° C, lasting several days, referred by some observers to shock due to operation; disturbance of the sensory nerves, represented by headache, and pains of the spinal nerves ; trophic disturbances in the form of bed sores; psychic disturbances in the form of delirium and persistent insomnia. ^Jonnesco: Op. cit., Brit. Med. J., Nov. 13, 1909, 1396. ^ Alessandri : ' ' Gli accidenti nervosi rachianestesia, ' ' II Morgagni, Aug. 24, 1909. SPINAL ANALGESIA AND SPINAL ANESTHESIA 583 Attention is called to the fact that certain disturbances which have been attributed to the stovain may also be referable to faulty puncture of the medullary canal or puncture at an unsuitable spot. Intense headache, dizziness, nausea, vomiting, rigidity of the neck, tenderness to pressure over the cervical vertebrae, and pain in the small of the back constitute a symptom-complex known as meningism — due to irritation of the meninges. Sleeplessness, lasting sometimes for as long as 7 nights, has been re- ported as following subarachnoid analgesia. Postoperative fever, with or without chills, the temperature some- times running as high as 102° F., in some instances follows the injec- tion of tropococain, the fever being a manifestation of irritation of the heat center of the brain. Headache, retention of nrine, and rise of temperature are seldom noted, according to Jonnesco, when his method is employed, and when they do occur they are of short duration. He has observed headache in 6.25 per cent of cases, but it is not severe, and disappears in a few hours after operation. Transitory retention of urine was observed in 4.5 per cent of cases. In no case did the temperature reach 104° F. Post- operative vomiting has rarely been observed by him, and he has never seen postoperative analgesia paralysis. Hoseman,^ in discussing the after-effects of lumbar analgesia and their control, calls attention to the importance of measuring lumbar pressure. This serves to show that headache as a sequel to lumbar anal- gesia is always associated with changes of pressure, which is rarely in- creased, but frequently diminished. Where the pressure is increased the headache is favorably affected by the withdrawal of spinal fluid; when it is decreased, the introduction of fluid in the form of subcutaneous salt infusion and enemata is serviceable. The introduction of these meas- ures in the Eostock Surgical Clinic obviated the severe after-effects of lumbar analgesia. It has been claimed by a number of writers that albuminuria is one of the after-effects of spinal analgesia. Babcock ^ failed to corroborate this statement, never having observed any clinical evidence of irritation of the kidneys. My own experience is in keeping with that of Babcock. As a routine practice the urine is examined on the day following the injection, and the findings, with regard to albuminuria, are uniformly negative. Various motor manifestations have been noted. Among these may be mentioned paralysis of one or both abducens, the trochlearis, and some- times the oculomotor muscles, coming on from 4 to 18 days after the ^Hoseman: Verhandl. d. deutsch. Ges. f. Chir., 38 Kongress 1909, 17. - Babcock : ' ' Spinal Anesthesia, a Clinical Study of 658 Administrations, ' ' Fenn. Med. J., Aug., 1909. 584 ANESTHESIA analgesia, and disappearing spontaneously in from 21 to 36 days. Par- eses of the legs sometimes remain for a number of hours, as may also those of the rectum and bladder. Lusk ^ correlated the reported cases of paralytic sequels of the lum- bar injection of spinal analgesic agents, finding quite a number of in- stances. "These paralyses," he says, "became apparent either closely consecutive to the recovery of the patient from the effects of the anes- thetic, or else later after an interval of complete restoration of function to the patient. They are regarded as due either to trauma inflicted on the nerve structures by the puncturing needle, or to some irritative action of the solution injected. It can be seen that paralyses attributable to the former cause must be limited to the lower half of the body, and that their onset, as in the case of any severe nerve injury, ought to be immediate. The late occurrence of a paralysis would seem to be at total variance with a traumatic origin, and might consequently be regarded as characteristic of an irritation by the anesthetizing drug. In support of the latter proposition is the fact that paralysis of the upper extremity and more frequently of the eye muscles, following the lumbar injection of a spinal anesthetic, which could by no possible logic be attributable to the traumatism of a lumbar needle puncture, are characterized by a late onset. These late occurring paralyses are sometimes permanent." Persistent paralyses are very rare, according to Fisher.^ When they do occur, according to this writer, they are referable to imperfect asepsis (spinal meningitis), or to the injection of a too highly concentrated, irri- tative solution. In my first paper,^ under the head of after-effects, the statement is made that in all cases whatever after-effects were noted were of a tem- porary nature. In only one case (cited by Lusk) were there any seri- ous symptoms following operation. In the case referred to the patient, a male child 7 years of age, was in a very poor general condition, with a marked lumbar kyphosis, and a large psoas sinus with small inguinal opening. Operation consisted in the enlargement of the sinus, curettage of the bodies of the third and fourth lumbar vertebrae. The cocain solution, 9 minims of a one per cent solution, was injected to the right, between the twelfth dorsal and first lumbar vertebrae, thus avoiding the site of the spinal curvature. In 9 minutes after the injection, analgesia was present over the entire body, with the exception of a space bounded behind by the posterior fontanelle, in front by the point of the chin, and laterally on each side by the angle of the jaw, the malar bone, the temporal ridge, and the parietal boss. ^Luak, William C. : "The Anatomy of Spinal Puncture, with Some Con- siderations on Technique and Paralytic Sequels," Ann. of Surg., Oct., 1911. ^Fisher: " L 'Anesthesie rachidienne, " These de Paris, 1911. 'Bainbridge: 0-p. cit., Med. Bee, Dec. 15, 1900. SPINAL ANALGESIA AND SPINAL ANESTHESIA 585 Some nausea and vomiting occurred for a few minutes after the injec- tion. During the operation the patient was free from pain, and showed no sign of nervousness. He answered questions and manifested a full command of his faculties. Analgesia disappeared in 1% hours. Before operation, the temperature was 98.4° ; pulse, 126 ; respiration, 34. One hour after operation, temperature, 100. G° ; pulse, 108; respiration, 36. The patient vomited twice during the night. The pulse was good. The day following the operation the child was restless at intervals, and cried out. An ice cap was applied, sodium bromid given in small doses, and the bowels thoroughly opened. The second day after opera- tion the patient seemed stupid, and was apparently unable to express his desires in words. He did not move the right arm and hand, and the legs were drawn up. There was a slight elevation of temperature, with weak and rapid pulse. The third day was marked by a continuation of the stupidity, failure to talk, and slight movement of the right arm. Strych- nin and digitalin in small doses were administered hypodermatically. Improvement then began to be noted, ability to move the right arm slowly returned, the legs could be extended, and the patient began to talk. One month after operation he was in excellent condition, and bet- ter than before operation. In a later paper ^ the following statement occurs : "Of the many scores of cases upon which I have operated in this way, the ages have varied from 4 months to 67 years. With cocain as an agent, and with my present technique, I have had no failures and no serious after-effects. Many of the patients have been under my observation for several years after the operation without any deleterious effects being noted. The prophesied evil to the cord — which the needle should never touch — has not been seen in any cases coming under my observation." This early experience, which was almost exclusively with cocain, has been corroborated, in the main, during the years which have elapsed since the introduction of the method. In 1,065 cases, in hospital and private practice, and with other agents as well as with cocain, I have had only 1 death (with the diffusible stovain solution, probably due to status lymphaticus; one case of temporary partial paralysis (see p. 584); one case of failure to induce analgesia, due to idiosyncrasy (see p. 623) ; one case of failure due to so-called "dry spine" (see p. 624) ; and two cases, with alypin, in which there was considerable respiratory depression. In all the other cases there were no accompanying or postoperative symp- toms of permanent or serious moment. ^Bainbridge: "Further Eemarks on Spinal Analgesia." Eead before the Med. Soc. of the Co. of Westchester, Yonkers, March 15, 1904. 586 ANESTHESIA INDICATIONS AND CONTEAINDICATIONS The extremes of opinion with reference to the safety of spinal anal- gesia have been expressed by Murphy ^ and Jonnesco.^ The former said: "The mortality of spinal analgesia is such as to cause it to be abolished as an analgesic of choice, if not sufficient to cause statutory enactments against its use." The latter holds that there are no contra- indications for "general spinal anesthesia," which, according to his be- lief, is absolutely safe, has never caused a death nor produced any im- portant complications, early or late, is infinitely superior to inhalation anesthesia, is within the reach •)f all, and may be employed with any patient. Between these two extremes of opinion may be found various degrees of conservatism and radicalism. Eeference to the views of a few who have written upon the subject will serve to show how widely divergent they are concerning the indications and contraindications for spinal analgesia. Bier, speaking before the German Medical Congress in April, 1909, cautioned against indiscriminate resort to spinal analgesia, and ad- vised its restriction to pelvic operations and operations upon the lower extremities. According to Buxton,^ the consensus of opinion narrows the limits of the employment of this method, excluding from its use the following individuals: "The wounded in war, children, persons over 65, syphi- litics, those who have some infective or septic disease, sufferers from serious heart or nerve lesions, arteriosclerosis, the nervous and the alco- holic, those who have albuminuria, and diabetics." "This list," he con- tinues, "comprises the opinions of various experts and narrows the field very considerably, but it is only fair to say that many able surgeons who adopt the spinal puncture are prepared to risk the dangers of the conditions named and do not select their cases." Matas* limited the indications: (1) To adults, and to reasonable persons who have good self-control, thereby excluding children, hysteri- cal patients, and the insane; (2) to patients in whom the methods of local or regional anesthesia are inapplicable; (3) to patients suffering from emphysema, advanced asthma, chronic bronchitis, and other res- ^ Murphy, John B. : "The Practical Medicine Series," 2, Editorial note, 28; "General Surgery," 1909. == Jonnesco : Op. cit., Brit. Med. J., Nov. 13, 1909. 3 Buxton, Dudley W. : " Discussion on Spinal Analgesia, ' ' Section on Phar- macology and Therapeutics, Brit. Med. Assn., Brit. Med. J., Sept. 18, 1909, 786. 4 Matas, Eudolph : ' ' Local and Regional Anesthesia with Cocain and Other Analgesic Drugs, Including the Subarachnoid Method, as Applied in General Surgical Practice," Phila. Med. J., Nov. 3, 1900. SPINAL ANALGESIA AND SPINAL ANESTHESIA 587 piratory affections in whom a general inhalation anesthetic is absolutely contraindicated ; in advanced cardiac cases with degenerative lesions (on account of the possible depressing effects of the injection and ex- citement of the circulation) ; (4) in the majority of cases in which the painful part of the operation is not likely to be prolonged beyond one hour arid a half. Matas also acknowledges its indication in labor, espe- cially in nephritic patients. Babcock ^ employed spinal analgesia "in the most serious types of dis- ease requiring operation below the level of the diaphragm where the pa- tient suffered from severe shock, hemorrhage, marked sepsis or toxemia, or in conditions of extreme debility." Gray ^ has found the method to be particularly indicated in many cases of abdominal surgery, preventing shock and reducing mortality 25 or 30 per cent. Leedham-Green,^ after an exhaustive experience with the method, found it to be indicated in dealing with gravely debilitated patients, such as those suffering from chronic intestinal obstruction, extravasation of urine, senile gangrene, and the like, where the disturbance occasioned by a general anesthetic often robs the patient of his chance of recov- ery. He also found it to be of great value for catheterization of the ureters in patients with highly sensitive bladders, as in cases of tubercu- losis. Canny Eyall * uses the method for operations on all parts of the body. Craniotomy, excision of the sympathetic ganglia, extirpation of the larynx, and excision of one-half of the tongue, with removal of the glands from both sides of the neck, are some of the operations performed by him under spinal analgesia. Summing up the findings of many surgeons, it would seem that the method is generally conceded to be contraindicated in persons suffering from concomitant affections of the heart, lungs, and kidneys; from defi- nite lesions of the nervous system, especially of the spinal cord; from sepsis or pyemia; from recent lues, and, according to some, from the later manifestations of this disease. Persons already in shock, or col- lapse, are not suitable subjects for this method, and for this reason it is considered by some to be unsuitable for war surgery. It may be generally conceded, also, that, as a rule, the method should be employed for operations below the costal border, being especially indi- cated for operations upon the genital organs, perineum and rectum, and ^Babcock: Op. cit., Penn. Med. J., Aug., 1909. ' Gray : ' ' Indications for the Employment of Spinal Anesthesia in Ab- dominal Surgery," Brit. Med. J., Sept. 2, 1911. ' Leedham-Green : "Discussion on Spinal Analgesia," Section on Pharma- cology and Therapeutics, Brit. Med. Assn., Brit. Med. J., Sept. 18, 1909, 789. * Eyall: Brit. Med. J., June 19, 1909. 588 ANESTHESIA upon the lower extremities. As is well known, many surgeons do not subscribe to these limitations. The method has been found uniformly satisfactory in a considerable number of infants and young children in whom I have employed it. The youngest child operated upon by me under spinal analgesia ^ was a male 3 months old, in very poor general condition, suffering from double inguinal hernia, with danger of incarceration. Incarceration finally oc- curred, and the patient was operated upon under chloroform anesthesia. Active stimulation was necessary during the narcosis. The patient re- covered from this operation, but the other side became strangulated some days later. The patient was in such poor general condition, in addition to having developed bronchitis and having undergone an operation so shortly before, that it was deemed unwise to resort to a second general anesthesia. Spinal cocain analgesia was employed March 19, 1901. Point of puncture, between third and fourth lumbar vertebras; amount of cocain, 6 minims of a one per cent solution. Injection, 11 :33 a. m. Analgesia to the level of the diaphragm at 11 :40. Operation begun at 11 :40i/2- Infant began to cry before the needle was inserted in the back, and continued to cry until the feeding bottle with a small quantity of milk was allowed. Vomited once. There was no pain, and the patient remained quiet the greater part of the time. The sac was separated and opened, exposing intestines, the appearance of which confirmed the necessity for operation. When the constricted neck of the sac was en- larged a coil of intestine came down. Difficulty was experienced in re- ducing the intestine, and a few breaths of chloroform were given for the purpose of still further relaxing the muscles and quieting the child, who, by this time, had become frightened at the efforts to place the loop of intestine back in the abdominal cavity. The suturing of the abdominal wair and the completion of the operation were accomplished under the analgesia from the cocain. At the end of the operation, at 12:15, the loss of the pain sense was complete to the level of the diaphragm. There was no vomiting from the time of the initial emesis until the chloroform was administered. To those present at the operation, it was apparent that a general anes- thetic would have proved fatal to the child. Perfect recovery resulted. The most striking report of the application of spinal analgesia in children comes from Gray,^ who published an interesting series of ob- servations in 300 cases in infants and young children, the youngest be- ing 12 hours old, the oldest 13 years. Of the operations performed, 190 ^Bainbridge: Op. cit., Archives of Pediat., July, 1901, Case XII. * Gray, H. Tyrrell: (1) "A Study of Spinal Anaesthesia in Children and In- fants, from a Series of 200 Cases," Lancet, Sept. 25, Oct. 2, 1909; (2) "A Fur- ther Study of Spinal Anaesthesia in Children and Infants," Lancet, June 11, 1910. SPINAL ANALGESIA AND SPINAL ANESTHESIA 589 were upon the trunk, and 104 upon the extremities. Failure to obtain anesthesia resulted in 10 out of the 300 cases. Of the first 100 cases, 9 children died subsequently from diseases for which they were operated upon. Necropsy showed no abnormality in the nerve roots, the cord, or its membranes. In the second series of 100 cases there were no deaths from the spinal analgesia. In the third series of 100 cases the author reports one death under analgesia. The patient was in such condition that operative relief seemed imperative, and death was practically certain under general anes- thesia. Necropsy in this case showed that both lungs were completely collapsed; that there was pneumothorax on both sides; that the left side of the diaphragm was extensively infiltrated, with malignant new growth extending into the left pleura; that there Avere several nodules on the under surface of the right side of the diaphragm and metastatic de- posits in various other regions; and that the growth from which the pa- tient was suffering was a retroperitoneal sarcoma, involving kidney, pancreas, etc. The outcome in such a case cannot be considered as cor- roborative evidence of the alleged contraindication of infancy and child- hood. In concluding his last report, Gray says: "Such disadvantages as are consequent on the use of this method are very greatly overshadowed by the advantages to the patient and surgeon in certain cases. I believe that spinal analgesia is urgently called for on all occasions where the after-progress of a case is likely to be influenced by shock during opera- tion, and often in cases when its employment is of definite assistance to the surgeon in doing his work as perfectly as possible." Waugh,^ of the Great Ormond Street Hospital for Sick Children, says concerning spinal analgesia in children : "So striking is the imme- diate result, as witnessed by the surgeon, that for my own part all opera- tions on children below the level of the fifth thoracic nerve involving considerable shock are unhesitatingly performed under spinal anesthesia as the anesthesia par excellence for such cases." "That I have been able," he continues, "to resect six inches of intestine for acute obstruc- tion in a baby eighteen hours old, perform a lateral anastomosis by suture in the ordinary way, and .send the child out of the hospital in a fort- night's time is a striking testimony to its value." He adds that he has completely abandoned the use of general anesthesia for children in all cases of acute appendicitis, intussusception, and acute intestinal obstruc- tion, which cases form no small share of the operative work in a large children's hospital. Preleitner,^ in Escherich's clinic, had an experience of -40 cases in ^ Waugh, George E. : Personal commmiicatioii, 1911. "Preleitner: Munch, med. Woch., 1905, 52. 590 ANESTHESIA children, with discouraging results. Fraenkel/ discussing Preleitner's paper, held that spinal analgesia does not eliminate the psychical factors, for which reason the method had not obtained a foothold in the surgery of children. Barker ^ excluded children from his list of patients, along with "ob- viously nervous and excitable people.'^ Gray,^ commenting upon such experiences, stated that they are en- tirely contradicted by his own experience. "From the psychical aspect," he says, "no more suitable patients for spinal anesthesia could be found, since ignorance is their safeguard against panic, and it may be stated generally that the younger the children the more satisfactory are they in this respect." The most troublesome age, in his experience, is between 2 and 5 years, children of this age being with greater difficulty kept quiet. Personal experience is in accord with that of Gray. As Attending Surgeon, New York City Children's Hospitals and Schools, ample oppor- tunity has been afforded me to test the utility of spinal analgesia, not only in infants and young children, but in the highly neurotic, epileptic, and idiotic. In one instance,* the patient, female, aged 4 years and 10 months, of very nervous temperament, being operated upon for umbilical entero- epiplocele, gave some hysterical manifestations during the operation, and cried as if in pain. Careful tests proved, however, that the analgesia was complete with reference to pain sense. ISTo serious accompanying or post-operative symptoms occurred in this case. In another case ^ of the same series, the patient, male, aged 9 years, was an epileptic, operated upon for congenital malformation of the glans and prepuce, with hypospadias. No pain or nervousness was noted in this instance. Of the cases reported in another paper,*^ the following features were noted: epileptic; highly neurotic; nervous temperament; feeble- minded, deaf and dumb, hydrocephalic; marked idiocy, with epilepsy; highly neurotic; marked idiocy, with epilepsy; highly neurotic; idiocy. Among the conclusions formulated in the last-named paper is the fol- lowing: "In neurotic patients there are often hysterical symptoms di- rectly following the completion of the injection, but, as a rule, in a few ^Fraenkel: Milnch. med. Woch., 1905, 52. ' Barker: Op. cit., Brit. Med. J., March 23, 1907. ^Gray: Op. cit., Lancet, Sept. 25, 1909. " Bainbridge : Med. Bee, Dec. 15, 1900, Case II. 'Ibid., Case V. "Bainbridge: Med. News, May 4, 1901, Cases I, II, VIII, XIII, XV, XVI, XIX, XXI, XXIV. SPINAL ANALGESIA AND SPINAL ANESTHESIA 591 moments a calm follows and the patient lies perfectly still." Subse- quent experience bears out this statement. It has been claimed that convulsions are apt to follow spinal punc- ture in epileptics. In personal experience with 16 epileptic patients operated upon under spinal analgesia, not one instance of convulsion on the table has been witnessed. No increase in nervous symptoms was noted in any case, and several patients were distinctly better for days after the injection. Many of these children have lived for years after- ward, and have died of other diseases, nothing being found abnormal with the cord or the nerve roots. The contraindication of age beyond 65 years does not hold in all cases. Weber ^ reported a case in which he operated upon a man of 84 years. Jonnesco's oldest recorded case in 1909 was 75. Barker oper- ated upon one patient 71 years of age. Many other instances are on record of operations under spinal analgesia in patients far past middle life. An early personal case ^ was that of a woman 67 years of age, who was suffering from complete procidentia, with beginning gangrenous changes in the lower part of the uterus, fatty heart, edema of the lower extremities and marked edema of the local parts, and suppression of the urine for twenty-four hours previous to operation. Ether was thought to be contraindicated because of the absence of urine; chloro- form had been tried, but the patient collapsed under it. Cocain spinal analgesia was resorted to, 35 minims of a two per cent solution being injected between the second and third lumbar vertebrae. Analgesia was complete below the clavicles in 15 minutes, and lasted 2 hours and 50 minutes. The operation lasted only 30 minutes, as, after scarification of the cervix and curetting, it was found possible to reduce the uterus inside the pelvis and to retain it there without further operative pro- cedure. The only unpleasant symptoms in this case were nausea a few min- utes following puncture, retching once or twice, and slight headache, with 3 degrees elevation of temperature the night after the operation. Eecovery was uneventful. Another patient, male, 66 years of age, was operated upon for in- flamed, irreducible right inguinal hernia, January 24, 1911. The hernia could not be held by truss, and gave repeated symptoms of impending strangulation. In addition to this the patient was suffering from ad- vanced arteriosclerosis, enlarged prostate, cystitis, and a double car- diac lesion, and gave evidence of an old healed process in the right lung. The operation was successfully performed under spinal analgesia, with ^ Weber: J. Am. Med. Assn., Feb. 9, 1900. '■' Case IV, of paper read before the Med. Soc. of the County of Westchester, Yonkers, March 15, 1904. 592 ANESTHESIA 2 c. c. of a three per cent stovain-dextrin solution, injected between the third and fourth lumbar vertebra. There was no nausea, no vomiting, or other untoward symptom, the patient read throughout the operation, and recovery was uneventful. A man 70 years old was operated upon by me August 4, 1911, under cocain spinal analgesia, with 18 minims of a two per cent solution, in- jected between the third and fourth lumbar vertebrfe. The patient for years had suffered from hypertrophy of the prostate, with the usual symptoms. He had had electrical treatment for 5 years, with temporary benefit. For a year he had been in a pitiable condition, passing urine almost constantly, in dribbles, with retention in the bladder of from 24 to 36 ounces of urine, and having to wear a urinary receptacle night and day. The urine was about 25 per cent by volume of pus and detri- tus, with blood casts and albumin. He was running several degrees of temperature when first seen, early in July, and was in very poor general condition. Arteriosclerosis of moderate degree added to the complica- tions. The patient was put to bed, the bladder washed out for a time, and the alimentary canal cleared. With preliminary medication of i/4 gr. morphin and 1/200 gr. nitroglycerin. Young's operation for prostatec- tomy was performed without difficulty. Analgesia was complete to the clavicles in 3 minutes, and remained so during the entire operation, which lasted an hour. There was slight nausea for a moment at the be- ginning of the operation, but this quickly subsided. There were no other unpleasant symptoms. The operation was at 12 :30 p. m. At 7 p. M. the temperature was 102.8°; pulse, 112; respiration, 24. At 10 p. M. the temperature was 101° ; pulse, 114; respiration, 30. At 2 p. M. the following day, temperature, 100.6°; pulse, 110; respiration, 28. At 6 A. M.^ temperature, 99°; pulse, 100; respiration, 22. At 3 p. M.^ tem- perature, pulse, and respiration were normal. Eecovery uneventful. Spinal analgesia has been employed in the most elaborate gynecologi- cal and general surgery, the variety of operation, in suitable subjects, be- ing no contraindication. Wertheim,^ in a paper read before the joint session of the Chicago Medical and Gynecological Societies, October 10, 1906, said: "For over a year we used, with exceptionally good results, lumbar anesthesia. We use for this purpose stovain with the addition of adrenalin. Even very old cachectic women with badly degenerated hearts bear this operation well by this procedure." Barker,^ in his third series of 100 cases, a number of which were very ^Wertheim: "The Radical Abdominal Operation in Carcinoma of the Cervix Uteri," Surg., Gyn. and Obst., Jan., 1907. * Barker: "A Third Eeport on Clinical Experiences with Spinal Analgesia," Brit. Med. J., Aug. 22, 1908. SPINAL ANALGESIA AND SPINAL ANESTHESIA 593 grave conditions, cited, as the worst general condition to be contended against, the case of a woman 48 years of age, operated on in the country for gangrene of nearly 5 feet of the small intestine strangulated by bands. The patient was pulseless, and cyanosed in face and hand, with pulse between 120 and 130. About 6 eg. (0.92 gr.) of stovain placed her in comfort in 5 minutes, 4 feet and 9 inches of black gangrenous bowel were excised, and the healthy gut anastomosed above and below, with perfect recovery. In obstetric practice the method is not infrequently indicated, and has been successfully employed by a number of European and American obstetricians, as stated in the section on history. Doleris and Malartic^ conclude that the uterine contractions be- come painless in from 5 to 10 minutes after the injection of from 1 to 2 centigrams of cocain, remaining practically painless, though per- ceptible, for a period of about 27 minutes after an injection of 71/2 milli- grams. Complete analgesia, according to these authors, has a duration of from 1 hour and 23 minutes to 2i/4 hours, with a dose of from 1 to 2 centigrams. The uterine contractions become energetic, more frequent, and of longer duration after the injection than before it, and in the interval between the contractions the uterus remains in a condi- tion of tension during a variable period. They found the bleeding to be much less than usual, and in a case of placenta prgevia the hemorrhage spontaneously ceased before the rup- ture of the membranes. The action of the cocain on the fetus, in their experience, was nil. Cesarian section has been successfully performed under spinal anal- gesia by Sinclair,- Hopkins,^ and Doleris.* Marx ^ recommended spinal analgesia in all cases in which the first stage of labor is prolonged. By the use of small doses, used as required, he has been able to carry a patient painlessly through labor of 8 hours' duration. The only case ^ in which I have employed spinal analgesia in ob- stetrics was for the delivery of a full-term child by means of high for- ceps operation. The patient, Mrs. H., 26 years of age, lived in a tene- 1 Doleris and Malartie: "Analgesie obstetrieale par injection sous-araeli- noi'dienne de cocaine, ' ' La Semaine vied., 1900, 243. 2 Sinclair: "Caesarian Section under Cocaine Ansestliesia, " J. of Obst. and Gyn. of Brit. Emp., Sept., 1902, 221. 3 Hopkins: "Case of Cassarian Section under Spinal Anesthesia," J. Am. Med. Assn., May 24, 1902, 1355. 4 Doleris and Malartie: Oi). cii., Conipt. rend. d. I. Sac. d'Obst., Cyn. et Fed. d. Paris, 1900, 328. 5 Marx: Med. Bee, Oct. 6, 1900, 521. 6 Bainbridge : Eeported before the Surgical Section, Am. Med. Assn., Atlantic City, June 4-7, 1912. 594 ANESTHESIA ment house, and this was her fifth confinement. Labor began at 6 :30 on the evening of February 23, 1901, the weak and ineffectual pains continuing until 2 :30 a. m. of February 34. The membrane then rup- tured, and the infant's heart beat became very weak, then practically inaudible. It" was determined to deliver the child by forceps, under spinal analgesia. The injection was made at 3 :35 a. m.^ 20 minims of a two per cent solution of cocain being introduced between the third and fourth lumbar vertebrae. At 3 :48 analgesia was complete to the level of the chin, and at 4 :20 the child was born. By 6 :55 analgesia had fully disappeared. The analgesia was so perfect that the mother went to sleep during the delivery, being unconscious of the birth of the child until she was awakened by its cry. Ehrenfest ^ calls attention to the following objections which may be urged against spinal analgesia for general obstetrical use: (1) It is not a harmless procedure. (2) Disagreeable symptoms inevitably follow the injection. (3) It may have a toxic effect on the child, such cases having been reported. (4) The analgesic effect may disappear just at the mo- ment when it is necessary and only the unpleasant sequelae, such as vomiting and extreme nervousness, remain. (5) The loss of the active help of the abdominal muscles is a very decided disadvantage. From the weight of conflicting testimony with reference to the indi- cations and contraindications for spinal analgesia, it may be deduced, in a general way, that, granting the need of operation, and the impractica- bility of local or regional analgesia, the indications for spinal analgesia are the contraindications for general inhalation anesthesia. So far as the character of the operative procedure is concerned, there are practi- cally no contraindications to the employment of spinal analgesia. With the modifications of injection fluid now in use, it may be said that no part of the body is under the ban of contraindication. Despite the im- provements of technique and the extension of domain, the method is employed more often as one of expediency than as one of choice. ADVANTAGES AND DISADVANTAGES Advantages. — The advantages of spinal analgesia may be stated cate- gorically and briefly as follows : (1) Very little apparatus is required. (2) The operative technique presents few difficulties, hence tlie method is easy of application. (3) The injection may be made by the surgeon himself, thus obvi- 1 Ehrenfest : "A Few Eemarks on the Use of Medullaiy Narcosis in Ob- stetrical Cases," Med. Bee, Dec. 22, 1900, 967. SPINAL ANALGESIA AND SPINAL ANESTHESIA 595 ating the necessity of an assistant. For emergency, military, and naval surgery this is a distinct advantage. (4) Analgesia is quickly inducted, from 4 to 10 minutes being suffi- cient, as a rule, for the induction of analgesia as far as the diaphragm. (5) The relative safety, as regards life, with good technique, skil- fully executed, is high. (6) Does not depress the heart, like chloroform, or cause pulmo- nary and renal complications, like ether, as these anesthetics are ordi- narily administered. (7) Insures physical quietude during operation, which is of dis- tinct advantage to the surgeon. (8) Insures the patient's aid, which may he desirable, as in cough- ing mucus or blood from the throat. (9) May save the life of patients who, because of contraindications to inhalation anesthesia, would be consigned to their fate without opera- tive relief. (10) Controls surgical shock by blocking off reflexes. (11) Obviates persistent postoperative retching and vomiting, which is of esi)ecial advantage in abdominal work. (12) Lessens postoperative pain. (13) Lessens postoperative restlessness which results from post- operative pain. (14) Diminishes the danger of postoperative pulmonary compli- cations. (15) Gives "abdominal stillness," emphasized by Jonnesco, Gray, and others, in connection with laparotomies. (16) Decreases mortality. Busse,^ upon the basis of experience with 1,232 cases of lumbar anal- gesia, points out the following advantages of this method as compared with inhalation anesthesia: (1) The blood pressure is not seriously affected. (2) Asphyxia is considerably less frequent. (3) Vomiting during the operation is less "common and less pro- fuse. (4) Vomiting after operation occurs less frequently. (5) Vesical disturbances are reduced to about one-third to one- half. (6) Deaths from pulmonary embolism seem to become less com- mon. Babcock ^ emphasizes the following advantages of this method over general anesthesia: ^Busse: PraM. Ergehnisse der Gehurts. u. Gyn., 1909, 1; also, CentralM. f. Gyn., 1910, No. 42, 1363. - Babcock ; Pen7i. Med. J., Aug., 1909. 596 ANESTHESIA (1) It reduces the mortality and morbidity of operations. (2) It insures physical quietude before, during, and after the opera- tion. (3) It secures complete muscular relaxation and a desirable peri- staltic stimulation. (4) It increases the patient's comfort and resistance. Disadvantages. — The disadvantages of spinal analgesia have been variously estimated, from none at all to an overwhelming number, by the enthusiastic advocates of the method on the one hand, and its un- qualified opponents on the other. By conservative opinion they may be summed up categorically and briefly as follows: (1) Unpleasant accompanying and postoperative phenomena, which, despite all precautions, may occur. (2) Possible dangers from the analgesic agent ^jer se, which, though not so frequent as formerly, do nevertheless occur, and have always to be borne in mind. (3) Uncertainty as to the length of the analgesia, which may wear off before the operation is completed. (4) Uncertainty as to the exact amount necessary to produce the desired effect in a given case. (5) Absolute commitment of the surgeon to the consequences of the dose injected, the effects of which, if untoward, cannot be controlled, as in the case of a general anesthetic, the dose of which may be regulated to suit the exigencies of the individual case. (6) Consciousness on the part of the patient, and the consequent possibility of psychic pain, nausea, and other disturbances, especially on the part of nervous individuals. (7) Incomplete muscular relaxation, which may occur when relaxa- tion is desirable. (8) Failure to obtain sufficient cerebrospinal fluid to warrant mak- ing the injection, sometimes attributed to so-called "dry spine," and occurring at times in the experience of skillful operators. (9) Possible injury to and irritation of the spinal cord and nerve roots. DEATHS It has been repeatedly stated that death statistics are of no practical value in determining the direct toxic working of the drugs employed for the induction of spinal analgesia, the question being mainly one of dosage. Deaths have been reported in connection with each of the drugs in common use, whether justly attributable directly to the action of the drug in any case being a debatable point. It is fair to assume that other factors are to be considered in connection with fatalities re- SPINAL ANALGESIA AND SPINAL ANESTHESIA 597 suiting from spinal analgesia. For all surgeons, except, possibly, the few peculiarly expert operators who recognize no limitations to the method, the selection of the subject for spinal analgesia must exert con- siderahle influence over the mortality record. The entire management of the case, including the surgical interference, bears a direct relation- ship to the safety of the method. Despite every possible safeguard, how- ever, deaths have occurred, and will doubtless continue to occur, with this as with every other method. Chiene ^ collected the reports of over 12,000 cases, with 22 deaths, or, roughly, 1 death in 570. He holds that, if the cases be analyzed in which death occurred, it will be found that very few can be attributed solely, or even partially, to the anesthetic. In analyzing the table of statistics given by Strauss,^ in which the latter collated 22,717 cases, with 46 deaths, Chiene found that 25 of the 45 deaths reported oc- curred when cocain was iTsed, which works out at 21 deaths in 15,842 cases where other drugs were employed, or 1 in 754. Only 3 of these were stated to be clearly due to the analgesic agent, or 1 in 5,282, and 9 more seemingly in connection with the agent; in all, 1 in 1,320. Compared with results obtained in a similar number of cases by gen- eral anesthesia, Chiene considered the above figures not so unfavorable as some writers have claimed. Jonnesco ^ gives the following statistics : From July 5, 1908, to Nov. 8, 1909, 758 cases were operated upon by Jonnesco or his assistants. Two cases in London and 23 in America bring the total to 783, of which 195 were superior dorsal and 588 dorsolumbar injections. If to this number be added 603 earlier lumbar analgesias, he has a record of 1,386 rachianesthesias, without mortality. In a later communication Jonnesco * gives the following personal sta- tistics : One thousand and five cases, from Jiily 8, 1908, to September 29, 1910, including 238 high analgesias (operations on the head, neck, su- perior extremities, and thorax), and 267 low analgesias (operations on the abdomen, pelvis, perineum, and inferior extremities). These statis- tics include 2 cases operated upon by Jonnesco in London and 23 in America. The ages of the patients varied from 1 month to 82 years. He had no deaths, he avers, due to the method, in the 2 years. Two fatal cases among high analgesias occurred among his Eoumanian colleagues, but these were referable to overdoses of stovain or strychnin. » Chiene : Op. cit., Brit. Med. J., Sept. 18, 1909, 785. ^Strauss: "Der Gegenwartige Stand tier Spinalanalgesie, " Deutsch. Zeit. f. CTiir., July, 1907, 275. =' Jonnesco: Atn. J. of Surg., op cit., 1910, 29, 33. ^Jonnesco: "La rachi-anesthesie generale, " B,ev. de Therapeut. med.-chir., Dec. 1, 1910, 798. 598 ANESTHESIA Kohler ^ collected 7,780 cases, with 12 deaths. Chaput ^ knew of no deaths among 7,000 cases. Tuffier ^ reported one death (not posi- tively attributable to the analgesia) in 11 years. Gray * reported one death in his series of 300 cases in children. Barker ^ formulated a table of the results at 5 British hospitals working on exactly the same princi- ples and technique, and with the same instruments and solutions care- fully prepared. This table represents 3,354 cases, including 775 cases under his own observation, in which there were only 3 deaths, or 0.1 per cent. Michelsson,*' discussing the various attempts to calculate the mortality of spinal analgesia on the basis of statistical compilations, gives the fol- lowing divergent results : Tomachewski calculates the mortality of spinal analgesia as 1:17847; Strauss, 1:2524; Chiene, 1:570; Hohmeier, 1 : 200. The figures of Strauss are held by Michelsson to be nearest the truth of the matter, although the mortality percentage is stated a little too high, omitting cocain analgesia, the mortality amounting to about 1:3500. In a personal experience of 1,065 cases, covering an extensive variety of operations upon patients ranging in age from 3 months to 70 years, there has been one fatality.^ This might easily be attributed to other causes (see pp. 585, 625). It is worthy of note, in connection with the subject of mortality due to the subarachnoid injection of anesthetic agents, that Engsted^ has reported the successful use of ether as an antidote to cocain and other drugs employed as local or spinal analgesics. He has been able, by this means, to revive patients who were practically in extremis. The best results are obtained, he holds, when ether is administered to the degree of mild surgical narcosis, or even less. A mask is employed, and the vapor given by the drop method, thus preventing adding to the danger by excluding air from the lungs already engorged with venous blood. ^Kohler: Deutsch. Zeit. f. Cliir., 1909, 16. -Chaput: Brit. Med. J., May 30, 1908, 1330. * Tuffier: Personal communication, March, 1911. ••Gray: O'p. cit., Lancet, June 11, 1910. = Barker: Brit. Med. J., March 16, 1912, 597. *Michelson: Op. cit., Ergebnisse d. Chir. und Ortlio., 4, 1912. ■^ Bainbridge : "Spinal Analgesia — Development and Present Status of the Method, with Brief Summary of Personal Experience in 1,065 Cases," J. Am. Med. Assn. Read before the Section on Pharmacology and Therapeutics, in joint session with the Section on Pathology and Physiology, American Medical Associa- tion, Atlantic City, June 6, 1912. ^Engsted, J. E. : "Ether: An Antidote of Cocain and Stovain Poisoning," J. Am. Med. Assn., March 19, 1910, 964. SPINAL ANALGESIA AND SPINAL ANESTHESIA 599 ANALGESIC AGENTS The Therapeutic Committee of the British Medical Association ^ in- vestigated the following local analgeyic agents: stovain, novocain, tropa- cocain, beta-eucain, alypin, beta-eucain lactate, nirvanin, holocain hy- drochlorid, acoin, orthoform (new), and anesthesine. (See Chapter XX.) Among the points to which especial attention was directed in this investigation was the suitability of the agent for medullary narcosis. Preliminary experiments reduced the list to 4, viz. : stovain, novocain, tropacocain, and beta-eucain lactate, which were subjected to further investigation. After comparing these drugs one with the other, the conclusion was reached that novocain is the most satisfactory for gen- eral use. "Its anesthetic action is equal to that of cocain, and its tox- icity and general destructive power on the tissues are very much less." Of the four drugs mentioned in the above report, stovain, novocain, and tropacocain are most generally used, though some operators, myself among the number, still find, at times, a place for cocain. Various modi- fications of tlie analgesic solution and its preparation have been adopted. A few are mentioned here, but more are given in Chapter XX. Cocain, tropacocain, stovain, and novocain are considered in the or- der of their introduction for purposes of spinal analgesia, and not with reference to their relative merits. Personal experience with other agents, eucain and alypin, for example, does not warrant devoting to them fur- ther consideration. Eucain was discarded because it gives a "patchy" analgesia, and alypin because it depresses respiration. The analgesic agents most commonly employed are variously modi- fied, the purpose being to produce a fluid of the same, heavier or lighter specific gravity, as compared with the cerebrospinal fluid. The injec- tion fluid, thus modified, is more or less difl!usible, according to its rela- tive specific weight, and, as a consequence of the relative diffusibility, the analgesia produced is more or less controllable as regards its extent. The various analgesic solutions may be classed, according to their relative specific gravity, as follows : ( 1 ) Analgesic agent, plus water, plus alcohol; (2) analgesic agent, plus water; (3) analgesic agent, plus water, plus cerebrospinal fluid; (4) analgesic agent, plus cerebrospinal fluid alone; (5) analgesic agent, plus water, plus normal salt solution; (6) analgesic agent, plus water, plus dextrin, glucose, or gum arable. To any of the above may be added, if desired, adrenalin or some sim- ilar product, as employed by Bier, Gray, and many others, or strychnin, as suggested by Jonnesco. ^ Le Brocq : ' ' Keport on the Local Anaesthetics Recommended as Substi- tutes for Cocaine," Brit. Med. J., March 27, 1909. 600 ANESTHESIA Solutions of lighter specific gravity than the cerebrospinal fluid are generally called diffusible, whereas those of heavier specific gravity are called non-diffusible solutions. To the former class belongs No. 1 ; to the latter, No. 6. Cocain.^ — During the early days of spinal analgesia cocain was the agent most commonly employed, but because of the various fatalities and the many unpleasant accompanying and postoperative phenomena which marked the experimental stage it has been pretty generally abandoned. Allen 2 says : "Since 1899, when Bier's first work appeared, cocain has gradually given way to the less toxic and equally effective stovain, novocain, or tropacocain, and it is now never used." He considers that it has no place in spinal analgesia. With this view probably the ma- jority of surgeons are in accord. A more favorable opinion of cocain is expressed by Filliatre,^ who declares that this agent, employed by his method, is absolutely devoid of danger. His method, which he has employed in 1,500 cases, consists in first withdrawing 30 c. c. of cerebrospinal fluid, then injecting from 0.5 to 2 c. c. of a 2 per cent solution of cocain. This gives a dosage of from 1 to 4 eg. (0.15 -j- to 0.6 -[- gr.) of cocain. J. Garland Sherrill, of Louisville, Kentucky, has always found a two per cent solution of cocain quite satisfactory, never using over 15 minims as a dose. Charles Chassaignac (private communication), of New Orleans, has used cocain in doses ranging from 1/5 to 14 S^- E. Denegre Martin (idem), New Orleans, gives cocain the prefer- ence, employed in doses of 5 minims of a 4 per cent solution. Simon Marx (idem), New York City, mentions cocain as his second choice, stovain being first. He uses cocain in doses of 14 gr. In a rather extensive experience with cocain the results of Bain- bridge with this agent have been uniformly successful when the solution has been prepared according to his method. The dose employed ranges from 5 to 20 minims of a two per cent, and from 5 to 30 minims of a one per cent, solution. Cocain has been largely employed as a standard by which to gauge the toxicity of other analgesic agents. It is considered twice as toxic as tropacocain, about 7 times more toxic than novocain, and 6 times more toxic than stovain. While cocain is more toxic than other agents, needing, in conse- quence, more safeguarding, the resulting analgesia is more profound, and lasts longer, Avith correspondingly moderate dosage. The toxicity of cocain has been attributed by many writers to harm- 1 For further data, see Chapter XX. ^Boston Med. and Surg. J., 163, No. 19. ^ Ann. d. mal. d. org. genito-urin., 1909, No. 13. SPINAL ANALGESIA AND SPINAL ANESTHESIA 601 ful b_y-proclucts resulting from its decomposition l)y the heat iLsed in sterilizing this agent. Others contend that coca in is not decomposed by heat, and that the unpleasant phenomena which accompany its use in some cases result not from the cocain or its decomposition products, but from the water used in making the solution. Tropacocain.^ — It is claimed by some that analgesia occurs sooner with tropacocain than with cocain, and that it is of longer duration. Personal experience is that there is very little difference in these regards. The solution recommended by Willy Meyer ^ is as follows : Tropacocain hydrochlorate 0. 15 gm. (23^^ grs.) Sodium chlorid 0.06 gm. (1 gr.) Distilled water 10.00 gm. (23^ drs.) Fifty minims of this solution contain 5 centigrams (5/6 gr.) of tropacocain, which is the dose usually required. This dose gives an anal- gesia sufficient for an operation lasting 1 hour or longer. The Bier solution of tropacocain, so largely used, is put up in am- pules containing 1.3 c. c. of a 5 per cent solution of tropacocain, with adrenalin hydrochlorid, 0.00013 per c. c. The dose of tropacocain usu- ally given is 5 cgm. (5/6 gr.). Slajiner ^ employed spinal analgesia in 2,700 cases, during the years 1901-1909, in his capacity as chief physician to the Surgical Depart- ment of the Laibach General Hospital. In all these cases tropacocain was used (Merck's sterilized flasks), the usual dose being 0.07 gm. (1 + gr.)- Colombani,'* on the basis of 1,100 operations performed imder tropa- cocain analgesia, advocates as the usual dose 0.08 gm. (li^ + gr-)- Erhardt ^ recommends the addition of gum arable to the tropacocain solution used for spinal analgesia, in a dosage of three per cent gum to a one per cent tropacocain solution. The advantages of the addition are unmistakable, consisting in the diminution of the general toxic manifes- tations, and the prolongation of the anesthetic effect. The essential cause for the lessened toxic action is referable to the delayed absorption and the less immediate contact with the central nervous structures. Hertel," after having performed lumbar analgesia with watery solu- tions of tropacocain, recommends the addition of gum arable, which he has already employed in 82 cases. Apparently the danger is diminished, 1 See Chap. XX, for a fuller discussion of tropacocain. =^ Meyer, Willy: Med. News, April 13, 1901. sSla.iiner: Beit. s. Min. CUr., 1910, 67. 4Colombani: Wiener Min. Woch., 1909, No. 39. 5 Erhardt: Miinch. med. Woch., 1908, No. 19, 1005.. eHertel: Miinch. med. Woch., 1910, No. 16, 844. 602 ANESTHESIA although not entirely excluded ; the analgesia seems to reach higher, and the number of failures is also apparently diminished. Stovain.^ — The Bier compound of stovain is as follows: Stovain. .- 4 per cent Sodium chlorid 0.11 per cent Epirenin borate 0.01 per cent Tufiier recommends a 10 per cent solution of stovain in normal salt solution. Chaput uses the following : Stovain 10 per cent Sodium chlorid • . . 10 per cent Distilled water 80 per cent The Stovain-Billon solution so largely employed is marketed in am- pules of 2 c. c, each cubic centimeter containing : Stovain 0.04 gm. (6/10 gr.) Adrenalin borate 0.00013 gm. Sodium chlorid 0.0011 gm. Each ampule contains 8 cgm. of stovain (1 1/5 gr.), so that a mini- mum or a maximum dose may be given. Barker's compound (stovain-glucose) is: Stovain 10 per cent Glucose 5 per cent Distilled water 85 per cent The glucose was added by Barker for the purpose of obtaining a fluid of heavier specific gravity than the cerebrospinal fluid. By this means he believed it would be possible to localize the analgesia. Houghton " has contributed a report of 400 cases operated upon un- der spinal analgesia induced with the Barker stovain-glucose solution. From his previous experience-^ with other drugs, followed by the series of cases in which he confined himself to the use of the Barker solution, he concludes that the 5 per cent solution of stovain and glucose has given the most consistent and reliable results. In this series there was no case of failure to enter and to inject the spinal sac, no case in which the injection failed to induce adequate analgesia, and no case Avhich gave cause for any anxiety as to the safety of the method. In life-saving operations, such as amputation of the leg for diabetic gangrene, or 1 For further information on Stovain, see Chapter XX. 2 Houghton, J. W. H. : " Spinal Analgesia. Eeport of 400 Operations at the Military Hospital, Aldershot, " Lancet, Oct. 12, 1912, 1008. 3 Boyal Army Med. Corfs. J., Aug., 1908, and Oct., 1909. SPINAL ANALGESIA AND SPINAL ANESTHESIA 603 operaticn upon a patient with advanced cardiac disease, in wliieh neither chloroform nor ether is admissible, stovain can be used. In Houghton's experience there was absence of shock during operation, and tlie muscular relaxation was so complete that much less time was required for the com- pletion of the operation than with chloroform. The dextrin-stovain solution employed by Gray consists of stovain, 3 per cent, with de:;trin and suprarenin in saline solution. This solu- tion is placed upon the market in ampules of 2 c. c. each, one ampule being sufficient for the induction of analgesia to the diaphragm, and often above. The dose is 0.015 to 0.04 gm. (1/5 to i/o gr.) of stovain. The stovain-strychnin solution suggested and so extensively used by Jonnesco in the so-called high analgesia must be prepared in advance of the time of operation, inasmuch as the strychnin sulphate takes some time to dissolve. The amount of strychnin and stovain in the solution varies with the site of injection, the patient's age, and general condition. Jonnesco uses from 1 to 10 cgm. of stovain. Babcock, who advocates a solution of lighter specific gravity than the cerebrospinal fluid, uses the following combination, made by Mor- gan, of Philadelphia : Stovain 08 p. c. Ac. Lactic 02 Abs. Alcohol 20 Aq. dest q. s. 2.00 The alcohol content of this solution is reduced in strength about one- half by the admixture of the solution with the cerebrospinal fluid before it is thrown into the spinal canal. Lambotte, of Antwerp, and his assistants have employed stovain in over 1,800 cases, with uniformly satisfactory results. It may be of interest to note that at Sing Sing, the New York State prison at Ossining, stovain has been used exclusively since August, 1908, for operations below the level of the umbilicus.^ The results have been uniformly successful, with no deaths due to the anesthetic, in approxi- mately 400 operations performed by H. E. Mereness, Jr., and F. E. Let- tice. The Billon preparation is employed. Novocain.- — The novocain-suprarenalin solution advocated by Braun," who first suggested the addition of adrenalin to analgesic agents, is put up in ampules of 3 c. c. each, containing: ^Personal communication from Mereness, Feb. 23, 1913. ^ For f urtlier information on Novocain, see Chapter XX. 'Braun: Deutseh. Monatsli. Jah^iheill-., June, 1906. 604 ANESTHESIA Novocain 0.15 gm (1 to 1| gr.) Suprarenalin 0.000325 gm. (1-250 gr.) This is. equal to five minims of suprarenalin solution, 1-1000, to 3 c. c. of sterilized distilled water. Of this solution 2 to 3 c. c. may be used. Meissner ^ reports 600 lumbar analgesias from the Tubingen Surgical Clinic, in all but 40 of which novocain was employed, first in 5 per cent solution (2 to 3 c. c), later in 1 per cent solution (6 to 7 c. c). Eyall ^ reports having used novocain with the addition of strychnin, according to the Jonnesco method. Chaput ^ reports 405 cases treated with novocain, a 4 per cent solu- tion being used, without addition. The dose was from 0.06 to 0.08 gm. Hypodermic tablets, novocain, 1/3 grain, are on the market. Each tablet contains novocain 0.020 gm. In 988 of my 1,065 cases simple solutions of the analgesic agent — eocain, stovain, tropacocain, etc. — with water, were employed. In the remaining cases I have used various modified solutions, heavier and lighter, with and without the addition of adrenalin or other similar product. With no intention of condemning any of these modified solu- tions, I must confess that my preference is decidedly in favor of the sim- ple solution, with the analgesic agent sterilized according to the method herein detailed. With such a solution, prepared under personal super- vision, I am sure of the fluid injected into the subarachnoid space. If it were possible, as with Waugh, Gray, Barker, Babcock, and those who employ the ready-made solutions, to obtain the modified solutions fresh and dependable, the matter would be different. The fact remains, how- ever, that all of the solutions prepared and dispensed in ampules deteri- orate with time, and unless one is convenient to the source of supply there is always a doubt concerning the potency of the agent. STERILIZATION OF THE ANALGESIC AGENT* Many of the unfortunate results obtained in the early history of spinal analgesia were presumably due to improper methods of sterilizing the analgesic agent. This was certainly true of eocain. In order to overcome this difficulty various methods of sterilization have been de- vised, of which those of Tuffier, Roux, Murphy, and Bainbridge are ex- amples. ^ Meissner : Beit. Min. Chir., 64, No. 1. =* Eyall: Brit. Med. J., June 19, 1909. 'Chaput: Gaz. des Hopitaux, 1910, No. 48. "See Chapter V and Chapter XIII. SPINAL ANALGESIA AND SPINAL ANESTHESIA 605 The numerous special compounds have each a special method of preparation, which need not be detailed here. In 1899 the following method ^ for the sterilization of cocain was first employed by me, and since that time it has been found equally satis- factory for the other analgesic agents in general use. The simplicity of the procedure renders it valuable for emergency work, as well as for other surgical cases in which spinal analgesia is indicated. The method is as follows: Five grains of fresh cocain hydrochlorid crystals, carefully weighed, are placed in a sterilized measuring glass. Two drams of strong ether are added, and mixed thoroughly with the cocain crystals by means of a sterilized glass rod. The mixing process is continued until all the ether is evaporated. One-half to 1 ounce of warm boiled or filtered water or normal salt solution is then added. One-half ounce makes practically a 2 per cent solution, and 1 ounce a 1 per cent solution. Of the former solution 10 to 20 minims may be employed; of the latter, 10 to 30 minims. The drug is practically sterilized in its manufacture, and all that infects it is apt to be on the outside of the crystals. Careful bacteriologi- cal tests were made by me to determine the extent to which this process sterilized the cocain, and it was found that practically all ordinary organ- isms are destroyed. (See Fig. 256, p. 616.) The crystals do not deteriorate, as do the cocain and other solutions. It is advisable, however, if possible, to employ only fresh crystals, or to be sure that the crystals employed have been kept perfectly dry. In the preparation of the diffusible solution employed by Babcock pasteurization is resorted to instead of sterilization. SITES OF INJECTION The routes commonly adopted for spinal puncture are the lumbar and the sacrolumbar, the former being preferable in human beings and the latter in animals. For purposes of spinal analgesia the points of election are generally conceded to be between the spinous processes of the third and fourth or fourth and fifth lumbar vertebrge. It is easier to enter the canal at these sites, and the danger of injury to the cord is minimized. Lusk ^ emphasizes the conclusion, drawn from a series of anatomical studies, that "the only vertebral interspaces through which puncture of the subarachnoid space can be made with practical assurance that nerve structure will not be penetrated are the fourth lumbar and the lumbo- sacral, preferably the former." 1 Bainbridge : Op. cit., Med. Bee, Dec. 15, 1900. 2 Lusk: Op. cit., Ann. of Surg., Oct., 1911. 606 ANESTHESIA According to this author, "The anatomical findings in eleven dissec- tions of the arachnoid membrane, from the conns medullaris up into the cervical region, were condemnatory of the procedure of puncture within Fig. 243.— Diagram of Cross-section Opposite the Fourth; Lumbar Interspace. Below the lower border of the fifth lumbar vertebra nerve-roots were adherent to the arachnoid. Above this level the arachnoid was firmly adherent over the posterior surfaces of the laterally situated nerve-roots of the cauda equina, while mesially it lay loosely over the posterior surface of the nerve structures, to which it was connected by delicate trabeculse from about one-eighth to one-quarter inch in length, the shorter trabeculae occupying the more lateral position. (LuSk.) this area, as one attended with the greatest liability of penetrating the cord." Fig. 244. — Diagram of a Cross-section Through the Dorsal Spine. Showing how the arachnoid membrane may be adherent to the posterior surface of the cord, which was the predominating anatomical arrangement in this and the lower cervical regions in six out of ten dissections. The close contact between the arachnoid and dura is here illustrated. (Lusk.) In fifteen dissections the conus medullaris was found by Lusk to terminate in 11 cases at the level of the first lumbar vertebra, 3 times SPINAL ANALGESIA AND SPINAL ANESTHESIA G07 at the level of the junction between the twelfth dorsal and the first lum- bar vertebra, and once it reached to the lower border of the second .lumbar vertebra. The normal or usual termination is shown in Figs. 245 and 248. Of 11 dissections of the arachnoid membrane above the conus, in only three was there a complete posterior arachnoid space present all the way up into the cervical region, the channel being interrupted at intervals by transverse septa. In three dissections the arachnoid membrane was adherent to the posterior surface of the cord all the way from the conus up to the cervical region; in one it was completely adherent above the level of two inches above the conus, and in two above the levels of the fifth and seventh dorsal vertebrae respectively. ( See Figs. 243 and 244. ) From these findings Lusk concludes that, if the cerebrospinal fluid be constantly withdrawn as a result of mesial puncture at or above the level of the conus, in many instances the substance of the cord must be traversed by the needle and the fluid taken from the anterior portion of the arachnoid space. In all the 15 dissections Lusk found that the one site at which lum- bar puncture of the arachnoid space could have been made without lia- bility of injury to the nerve roots was mesially in the interval between the fourth and fifth lumbar vertebrae. The great tendency of the nerve roots to become adherent to the posterior wall of the arachnoid sac in the lumbosacral interspace, as well as for the subarachnoid space to become shallower in this region, rendered this the site of second choice. Despite the anatomical findings of Lusk and others who have studied the subject from this point of view, injections have been successfully made at higher levels than those above indicated. Morton,^ in two cases, injected between the last dorsal and first lum- bar, but abandoned this site as being unnecessary. Tait and Caglieri - (see p. 561) reported having injected cocain into the sixth cervical space, without untoward effects. Jonnesco,^ who at first advocated piercing the column "at all levels," later abandoned this procedure and confined himself to two sites : . ( 1 ) superior-dorsal, between the first and second dorsal vertebrae, and (2) dorsolumbar, between the twelfth dorsal and first lumbar vertebrae. "1 had already been convinced by experience," he said, "that spinal anes- thesia was not so regional as I had believed, and that mediocervical punc- ture was as useless as it was dangerous. It favors the appearance, of bulbar phenomena — nausea, vomiting, pallor of the face, momentary ^Morton: Am. Med., Aug. 3, 1901. ='Tait and Caglieri: Op. cit., Trans, of the Med. Soc. of the State of Cal., April, 1900; also, J. Am. Med. Assn., July 7, 1900. ^.lonnesco: Brit. Med. J., Nov. 13, 1909; also, Hevue de therap. med.-chir., Dec. 1, 1910, 798. Fig. 245. — Spinal Cord Enclosed in Unopened Dural Sheath Lying Within Vertebral Canal. Neu- ral arches completely removed on right side, and partially on left, in order to expose dorsal aspect of dura. (Piersol.) m <-jS1^ Fig. 24G. — Posterior Wall of Verte- bral Canal Has Been Removed and Dural Sheath Opened to Expose Spinal Cord and Dorsal Roots OF Attached Nerves. (Piersol.) SPINAL ANALGESIA AND SPINAL ANESTHKSIA G09 stoppage of respiration, and so on — phenomena due to a too direct action of the anesthetic fluid upon the bulb. Tlieir occurrence may be avoided by making the puncture lower down between the first and sec- ond dorsal vertebrae, wliich produces as perfect and rlccp analgesia for Anterior roots of spinal nerves Dura, reflected Spinal cord covered with araohnoid and Fig. 247. — Upper Part of Spinal Cord Within Dural Sheath, Which Has Been Opened and Turned Aside. Ligamenta denticulata and nerve-roots are shown as they pass outward to dura. (Piersol.) 610 ANESTHESIA the segment of the hody comprising the head, neck, and upper limbs as is produced by the mediocervical puncture. I have therefore reduced sites of election for puncture or two." These are stated above. Canny Eyall/ one of the most enthusiastic advocates of the Jonnesco method for opera- tions upon the upper part of the body, makes the injection into the first dorsal space, and for operations upon the lower part into either the eleventh or twelfth dorsal spaces. He rarely uses lumbar puncture, since, in his experience, better results are obtained by making the injec- tion into the dorsal region. He finds no advantage in making a cervical puncture, for perfect analgesia lasting an hour or two can be obtained by injecting be- tween the first and second dor- sal spines. Gray - considers it unneces- sary to make the puncture higher than the interspace be- tween the first and second lum- bar vertebrae, the space between the third and fourth being best for routine work. Avamresco ^ varies the site of puncture according to the op- eration, as follows: (1) For operations on the perineum, ex- ternal genitals, and anus, be- tween the third and fourth lum- bar vertebrae ; (2) for operations on the inguinal region and lower Fig. 248. — End of Spinal Cord With Roots OF Lower Nerves Descending in Cauda Equina to Gain Their Respec- tive Foramina. (Piersol.) ^ Eyall: Op. cit, Brit. Med. J., June 19, 1909. - Gray : Op. cit., Lancet, Sept. 25 and Oct. 2, 1909. ^Avamesco: Lancet, 1901, 1, 637. Fig. 249. — Schematic Picture Showing Landmarks Used In Locating Space Between Third and Fourth Lumbar Vertebra. Fig. 250. — Schematic Picture Showing Needle Inserted Between Third and Fourth Lumbar Vertebra of the Spinal Canal, but below the Cord. 612 • ANESTHESIA extremities, between the first and second lumbar spines; (3) for opera- tions on the abdomen below the umbilicus, between the ninth and tenth dorsal spines; (4) for operations on the abdomen above the umbilicus, between the sixth and seventh dorsal spines. Babcock ^ injects in the second lumbar interspace for operations not involving tissues above the level of Poupart's ligament, or the first lum- bar or twelfth dorsal interspace, if intra-abdominal manipulations are required. Personally, I recognize no advantage by going into the subarachnoid space at a higher point than between the third and fourth lumbar verte- bra, though on several occasions, because of deformity of the spine, or for other reasons, the spaces between the first and second, and be- tween the second and third lumbar vertebrae, have been successfully en- tered. In cases where there is to be much pulling and tearing of the tissues of the abdomen, particularly in the upper part, I sometimes in- ject between the twelfth dorsal and the first lumbar. Analgesia of any part of the body, however, may be obtained by lumbar injection, plus the use of an analgesic agent of equal or lighter specific weight than the cerebrospinal fluid, or by employing a fluid of greater specific weight, plus the lowering of the patient's head. THE PATIENT Preliminary Preparation of Patient. — The operator who is to make the injection should apply the principles of psychotherapy to the patient some time before the operation, if this is possible. The indications for the method in the given case should be explained, and emphasis laid upon the advantages of this method over inhalation anesthesia. A clear un- derstanding of what is to be expected on the part of the patient is quite conducive to the successful application of the method. At any rate, the patient's confidence should be gained by the operator. This is particu- larly true of nervous and excitable persons. Even with children much can be accomplished in this way. N'ot infrequently a doll or other toy put into the hands of the child patient will divert attention and gain confidence, sometimes rendering an otherwise intractable patient quite docile. A hypodermic injection of morphin (% to ^4 g^-)? combined in some cases with atropin or hyoscin, may be given half an hour or an hour be- fore injection. It serves to tranquilize the patient and to make him less susceptible to any possible pain or discomfort contingent upon the initial procedure. Bromids instead of morphin may be given the day before, or nitroglycerin (1/200-1/100 gr.), given coincidentally with the spinal injection, may be advantageous. Strj^chnin (1/60 gr.) given at the time ^Babcock: Op. cit., Penn. Med. J.,' Aug., 1909. SPINAL ANALGESIA AND SPINAL ANESTHESIA G13 of the injection is supportive. Coml)inccl with nitroglycerin, it lessens the danger of headache, shock, and other disagreeal)le symptoms. No preliminary medication is given with children. Preliminary prepara- tion of the patient as re- gards diet, catharsis, etc., which is of so great im- portance in inhalation anesthesia, is not essen- tial in spinal analgesia. Patients coming into the hospital from the street, with no preliminary preparation in these re- gards, have been oj^erated upon as successfully, and with as few accompany- ing and postoperative phenomena, as have those who have been subjected to the most careful pre- paratory care. Generally speaking, however, atten- tion to no details which conserve the patient's vi- tality and comfort should be neglected. Position of Patient. — The position of the pa- tient while the injection is being made is impor- tant. One should sit evenly on the edge of the table, the feet hanging down. The arms are folded against the abdo- men. At the moment of the puncture the patient should bend the head down, as in Figure 259, and push against the abdomen with the arms in such way as to arch the back and separate the vertebrse as much as possible. In the case of chil- dren and infants, it is necessary for the attendant to see that this position is maintained. Fig. 251. — Patient in Sitting Posture Ready foe Spinal Puncture. 1 and 2, Highest points of crests of ilia; 3, spinous processes of third, fourth and fifth lumbar vertebrse. 614 ANESTHESIA The patient must be warned beforehand, and reminded at the time, to maintain this position, and not to straighten up or otherwise move until told to do so. Fig. 252. — Injection Being Made With Patient in Recumbent Position. If for any reason it is impossible to make the puncture with the pa- tient in the above position, it may be done in the recumbent posture, as shown in Figure 352. APPARATUS AND MATERIALS The apparatus and materials employed in the induction of spinal analgesia are shown in Figures 253 and 254. The apparatus for giving the injection of the analgesic agent con- sists of a syringe and two cannulas. The syringe, which is made by Ford & Co., of New York, is entirely of metal, including the piston, so that it expands uniformly upon boil- ing. It has a capacity of 5 c. c, the corresponding quantities in the two systems being graduated upon the piston. The cannula are made in two sizes, of three lengths; the points are ground short and beveled, with a cutting edge all round. The shank is of flexible metal, so that it will bend without breaking. The cannula slips on a ground joint, fitting accurately the handle, without washers or screws. The proximal end of the cannula is fitted with a handle which can be firmly grasped. ■ SPINAL ANALGESIA AND SPINAL ANESTHESIA 615 Through the cannula runs a stylet, the proximal end of which is rounded, knob-like, so that it can be pressed against the base of the index finger, adding firmness of grip. Fig. 253. — Table Containing Instruments and Materials Used in Giving Spinal Analgesia, (a) Glass with sterilized water; (b) empty glass in which to collect cerebro- spinal fluid (c) bottle of iodin for sterilizing the skin ; (d) graduate for preparing solu- tion; (e) bottle of collodion; (f) bottle of ethyl chlorid wrapped in sterilized gauze; (g) sterilized gauze and steriHzed cotton; (h) small can of strong ether wrapped in sterilized gauze; (i) dish of bichlorid solution: (j) two powders, 5 grains each, one of cocain and one of tropacocain; (k) two ampules containing stovain (suprarenin-glucose solu- tion) ; (1) two needles and syringe (Bainbridge) ; (m) small scalpel for making punc- ture; (n) clamp with piece of sterilized gauze for painting the skin with iodin; (o) glass rod for mixing. The instrument can be taken apart and thoroughly sterilized. Figure 255 shows the fine needle employed by Babcock. The syringe is a Luer syringe of 2 c. c. capacity, graduated in cubic centimeters and Fig. 254 — Bainbridge's Syringe and Needle. Fig. 255. — Babcock's Needle for Spinal Analgesia. millimeters. The obturator which comes with this needle fits perfectly around the opening at the end of the needle, thereby closing it entirely during the time it is being injected and until the obturator is withdrawn, F G Fig. -256. — Sterilizing the Apparatus. A, placing the drug in the graduate; B, adding ether to sterilize; C, mixing ether with powder into a paste; D, adding required amount of water to make given solution; E, testing syringe with sterile water; F, testing syringe; G, filling syringe with injection material. SPINAL ANALGESIA AND SPINAL ANESTHESIA 617 before the syringe is slipped into the hub for the injection of the analgesic agent. This needle is made by Charles Lentz & Sons, Philadelphia. In sterilizing the apparatus no soda or other alkalies sliould be era- ployed, nor should the analgesic agents be in any way allowed to come in contact with these substances, which destroy tlieir analgesic properties. The sterile implements and materials are placed upon a table covered with a sterile sheet until ready for use. Various needles, syringes, etc., have been devised and advocated, and are readily obtainable. The apparatus described above will answer all re- quirements of spinal analgesia. TECHmauE or injection The operator's hands are made aseptic in the usual manner. The site of puncture may be cleansed in the ordinary Avay, by scrub- bing, etc., or, if desired, it may be rendered aseptic, after the patient has been placed upon the table, by painting the skin with tincture of iodin. If preferred, the area may be painted an hour or so before operation, and again after the patient is placed upon the table. If the iodin method is employed, no preliminary washing should be resorted to unless it is done a sufficiently long time before the painting for the tissues to become thoroughly dry. If desired, the skin may be sponged with ether, which quickly evaporates, leaving a perfectly dry surface for the action of the iodin. This is not necessary, however, as the iodin is sufficient for purposes of antisepsis. The patient, in the position shown in Figure 351, with the puncture site painted with iodin, as shown in Figure 257, is draped with the sterilized sheet, as shown in Figure 258. This sheet has cut in it a hole or window (Fig. 258) large enough for purposes of injection. The oi3erator, in making his examination and identification of landmarks, runs no risk of contaminating his hands by contact with skin surfaces which have not been rendered aseptic. The site of puncture is now located in the following manner, as indi- cated in Figures 259, 2G0, and 261: (1) The highest points on the crests of the ilia are located by the hands, as shown in the figures. (2) The sites of the second, third, fourth, and fifth lumbar verte- brae are marked. (3) The thumb of each hand is placed in the space between the sec- ond and third, third and fourth, or fourth and fifth lumbar vertebrae. 618 ANESTHESIA according to the selection of site, at the mid-point between the two. One- half inch to either side of this point is the site for the puncture. The puncture point being located, the assistant plays ethyl chlorid on the area, or, if preferred, a preliminary injection of cocain or other local analgesic agent may be made. (See Fig. 360.) A small incision is now made through the true skin, which is ren- dered hemostatic as well as analgesic by the ethyl chlorid. The needle is passed through the incised skin and subcutaneous tissue, straight forward, as in Figures 250 and 361. It is then depressed, the point being made to go upward, forward, and in- ward, toward the median line. It is inserted from 11/^ to 3 inches, accord- ing to the thickness of the patient's flesh. When the needle is felt to impinge upon the bone surrounding the foramen, it is depressed a little more, and pushed forward, when it comes upon the ligamentum subflavum, then the dura mater. In piercing the ligament and dura there is a peculiar sensation like the popping of a membrane. This signifies the entrance to the sub- arachnoid space. The cerebrospinal fluid escapes, as shown in Figure 363, under ordi- nary circumstances. If it does not flow freely, something is wrong. The needle may not have entered the right place, or it may be clogged. A stylet should not be inserted into the needle. Another syringe should be Fig. 257. — Puncture Site Area Painted with Iodin. SPINAL ANALGESIA AND SPINAL ANESTHESIA 619 ready, and with this, if one cannot draw out blood or fluid, the needle should be withdrawn, and, after being rendered patent, be reinserted. It should be noted that there is considerable difference in spines with reference to the amount of cerebrospinal fluid, some being what is called "dry," with little fluid escaping upon puncture ; others, "wet,"' with an abundance of fluid under high tension. The quantity withdrawn de- pends upon the tension. If the fluid comes out with force more is withdrawn than when it is not under much pressure. I prefer not to proceed with the injection unless the fluid issues with at least an approximate quan- tity and tension. Gray ^ does not hold to this point. Discussing the general opinion that satisfactory analgesia will not result un- less there is a free flow of fluid, he says: "This is true enough in the main, but if, after pa- tience and perseverance, a free flow of fluid cannot be obtained, but only slow drops (oT if slightly blood- stained fluid only appears), I consider that the injec- tion should be attempted before making another puncture, provided cerebrospinal fluid has been seen. I have encountered this class of case on two or three occasions, when, in spite of failure to obtain a free jet, a perfectly satisfactory anesthesia has resulted from the injection." Donitz ^ and Dean ^ suggest that when the fluid flows scantily this is an indication for a larger quantity of the analgesic solution. ^Gray: Op. cit., Lancet, Sept. 25, Oct. 2, 1909. ^ Verhandl. d. deuisch. Gesellsch. f. Chir., 1905, 525-548. ^Brit. Med. Jour., 1907, 2, 869. Fig. 258. — Sterilized Sheet, Patient Draped, AND Window Made at Site of Puncture. Fig. 259. — Locating the Site for Puncture. Fig. 260. — Applying Ethyl Chlorid and Incising the Skin. SPINAL ANALGESIA AND SPINAL ANESTHESIA 621 In some cases, despite careful technique and repeated attempts, at different sites, no cerebrospinal fluid is obtainable. Such cases have doubtless led to the expression "dry spinp," but it is rather to be in- ferred that they come under the category mentioned by Gerstenberg and Hein, Lusk, and others. (See pp. 564 and 605 et seq.) A personal ex- perience with such a case is cited on page 624. The first few drops of fluid may be bloody, which may signify merely that a small quantity of blood has been carried in with the needle. If it Fig. 261. — Showing Direction of Needle About to Enter Spinal Canal. continues bloody, however, something more serious is to be considered. This rarely happens, but when it does the operation should be discon- tinued. Sometimes, when the fluid does not flow freely, it will do so if the patient will cough, thus causing more tension upon it. An uncontrollable patient, who will not remain still and quiet, should be held steadily while the puncture is being made, or the needle should be withdrawn at once. The injection of the analgesic agent should not be made unless the patient is perfectly quiet. The fluid is injected slowly, as shown in Figure 263. The obliquity of the passage of the needle has the advantage that no tract is formed for the fluid to follow as the needle is withdrawn. The body of the vertebra in front should not be touched with the needle, because of the presence there of a large plexus of blood vessels. 622 ANESTHESIA Fig. 262. — Cerebrospinal Fluid Escaping. When the needle is withdrawn a cotton and collodion dressing is ap- plied, as shown in Figure 264. If low analgesia is desired, for op- eration upon the lower part of the body, the patient may be allowed to sit up for a few minutes after the injection, or the head may be ele- vated. If high anal- gesia through lum- bar puncture is desired, for opera- tions upon the up- per part of the body, the head is lowered, or a fluid with lower specific gravity than the cerebrospinal fluid is employed. Having had no personal experience with the Jonnesco method of induc- ing high analgesia, no statement can be made with reference to the relative merits of the so-called high analgesia for this pur- pose, as compared with lumbar injection plus modified agent or position of patient. Babcock ^ prefers to use a small needle (Fig. 255), and to go in without the pre- liminary nicking of the skin. If the pa- tient has received no preliminary medica- tion the area marked off on the back is frozen by a spray of ethyl chlorid. The needle is intro- » Babcock: Op. cit., Penn. Med. J., Aug., 1909. Fig. 263. — Injecting Solution. SPINAL ANALGESIA AND SPINAL ANESTHESIA 623 duced through the line marking the injection point, at right angles to the skin, and about 2 millimeters to one side of the median line. The needle is carried steadily forward until the resistance of the ligamontum subflavum is felt, when the mandrin is withdrawn from the needle, which is then carried on through the dura. If high analgesia is desired, Babcock considers it advisable, before the injection is given, to so reduce the cerebrospinal fluid that it issues only in drops from the needle. The needle is cautiously rotated to make sure that the bevel point is en- tirely through the mem- brane. The syringe is then attached, and about 1 c. c. of cerebrospinal fluid is cautiously with- drawn to mix with and dilute the analgesic so- lution. The mixture is now steadily and rather rapidly injected, the needle with the attached syringe quickly with- drawn, and the patient immediately placed in the recumbent posture with the head slightly raised. This last point is of the utmost im- portance. In testing for analgesia, which begins in from three to ten minutes after the injection, one should bear in mind the difference between anal- gesia and anesthesia. (See Introduction, p. 555.) Fig. 264. — Cotton and Collodion Dressing on Puncture Point. ADDITIONAL ILLUSTRATIVE CASE REPORTS With the preliminary preparation, the necessary adjuvant medica- tion, and the careful technique, as outlined in the foregoing pages, there should be no difficulty with spinal analgesia, unless some anatomical anomaly or an idiosyncrasy be encountered. Occasionally, — very rarely, — one encounters a patient who possesses an idiosyncrasy with refer- ence to one or another, or perhaps all, of the spinal analgesic agents. Such a case was encountered by me recently, as was also one of so-called "dry spine.' Case of Idiosyncrasy. — H. C, female, aged 24. Consulted me in Feb- ruary, 1911, with reference to hernia and displacement of the uterus. Pa- 624 ANESTHESIA tient was anemic and nervous, and had an old healed tuberculous lesion of the lung. Otherwise in fair general condition. She requested that operation be performed under spinal analgesia. This was undertaken on February lA, 1911, no preliminary medication being employed. Spinal puncture was made, between the third and fourth lumbar vertebrae, and 30 minims of fluid withdrawn. An injection was made of 15 minims of a 3 per cent solution of novocain. After an interval of 15 minutes there was no analgesia, even in the feet. A second injection was made, this time with stovain, 13 minims of a 3 per cent solution being used. After waiting 20 minutes the site of operation was still sensitive. During all this time (40 minutes from the time of the first in- jection), the patient was in good condition, with only slight nausea and no vomiting. The pulse was 120, full and strong. The operation was abandoned for the day, it being thought unwise to subject the patient to a third injection. During the next three days she suffered from slight headache, but was otherwise in good condition. On February 17 another attempt was made to induce spinal anal- gesia. Cocain was used on this occasion, 15 minims of a 2 per cent solu- tion being employed. After 25 minutes there was no evidence of anal- gesia so far as pain sense was concerned. The patient was nervous to begin with, and became nauseated after the injection, but the pulse (120) was fairly strong. A second attempt was made, but, as there was no es- cape of fluid, no injection was made. On the assumption that the patient had an idiosyncrasy, it was de- cided to test the matter with local injections. ^Accordingly, 1 c. c. of a 2 per cent solution of cocain was injected at the site of ' operation, but without success. The patient became quite hysterical, and the entire mat- ter was abandoned. Patient was subsequently operated upon under gen- eral anesthesia. Upon further questioning, it was learned from the patient that in 1900 an attempt was made by Dr. Frederick Kammerer, of New York, to operate upon her for appendicitis under spinal analgesia, cocain being employed. No analgesia was obtained, and the operation was performed under general anesthesia. Case of So-called ''Dry Spine." — B. M., female, negro, aged 17. Oper- ation, Woman's Hospital, Philadelphia, January 25, 1912, appendectomy. Gangrenous appendix found to be walled off by adhesions. Kecovery un- eventful. This patient had Bright's disease and an old consolidation at the apex of one lung. For these reasons it was thought advisable to operate under spinal analgesia. An attempt was made to operate in this case under spinal analgesia, but without success. Puncture was made between the fourth and fifth lumbar vertebrae, but, only a tiny drop of fluid being obtained, injection SPINAL ANALGESIA AND SPINAL ANESTHESIA 625 was not made. A second attempt with another needle proving futile, puncture was made successively in the spaces between the third and fourth and second and third lumbar vertebra;. No fluid being obtained, the efl^ort at spinal analgesia was abandoned, and the operation was per- formed under inhalation anesthesia. Case of a Typical "Satisfactory" Analgesia.^ — L. L., female, aged 58, admitted to the New York Skin and Cancer Hospital, March 18, 1911, for operation for lipomata of the abdominal wall, papilloma of neck, angiomata of abdominal wall, and varicose ulcers of the legs. Opera- tion, March 20, 1911. The various growths were removed, and the ul- cers of the legs excised. Adjuvant medication : Strychnin sulphate, 1/GO gr. ; nitroglycerin, 1/200 gr. Analgesic agent : Glucose-adrenalin-stovain, one ampule, 2 c. c. ; stovain, 3 per cent. Analgesia extended to neck, and lasted for 1 hour and 55 minutes. There was no nausea, no vomiting, no headache, or other unfavorable symptom, and recovery was uninterrupted. Case of Typical Analgesia, hijection in Recumhent Position. — Fig- ure 262 represents the injection being given with the patient in the recumbent position. This patient was a male, B. N., aged 38 years. Operated upon for gangrene of the foot February 7, 1911, the foot being partially amputated. No preliminary medication. Stovain, 8 minims of a 3 per cent solu- tion, injected between the third and fourth lumbar vertebrae. Analgesia complete to the umbilicus in 8 minutes. No unfavorable symptoms. On February 24, 1911, amputation of foot, leaving os calcis. Sixteen minims of a 3 per cent solution of stovain in water employed. Within 2 minutes after the injection the patient was analgesic to the nipple line, and 5 minutes after the injection the operation was begun. No unfavora- ble symptoms. Patient manifested an interest in the entire procedure. An Additional Case (No. 1069), of Special Interest.^ — During the Clinical Congress of Surgeons of North America, held in New York City in November, 1912, a patient at the New York Polyclinic Hospital died after a lumbar subarachnoid injection of stovain, preparatory to the per- formance of an operation for hernia. P. H., Irish, male, age given as 50 years, probably 60 or more; chronic alcoholic. Came to my clinic at the New York Polyclinic Medical School and Hospital, October 18, 1912, seeking relief for a condition which ^ This is the case with which the technique is illustrated, Figs. 251 and 257 to 264. ^ Bainbridge : ' ' Spinal Analgesia — Development and Present Status of the Method, with a Brief Summary of Personal Experience in 1,065 Cases." J. Am. Med. Assn., Nov. 23, 1912, 59, 1855-1859. 626 ANESTHESIA proved, upon examination, to be right inguinal hernia, at times irreduci- ble, and causing great suffering. The man gave a history of having felt a sharp, tearing pain in the right groin, while operating a taxicab, about three months previous to coming to the clinic. Since that time he had been to several dispensaries in a vain search for relief. He had used a truss without success. Failing to obtain relief by other measures, he wished to be operated upon at once. From the general physical examination the patient was found to be in a very bad condition, as the result of the prolonged excessive use of alcoholic stimulants. The following conditions were present: general atheroma of the arteries ; renal insufficiency, due to chronic Bright's dis- ease; marked enlargement of the liver; myocarditis, with systolic mur- mur at the base ; emphysema ; rales over the bases of both lungs. A his- tory of chronic gastritis was also elicited. The patient's general condition was such that immediate operation was not deemed advisable. He was told, accordingly, to abstain from the use of intoxicants, and to refrain from lifting or straining; he was put upon a diet, tonics, etc., and was kept under observation for about three weeks. Despite the fact that only slight improvement followed this regime, he insisted upon operation. He was then admitted to the hos- pital on jS"ovember 14, and prepared for operation the next day. Because of the man's general condition, inhalation anesthesia was con- sidered contraindicated. He was prepared, accordingly, for operation "imder spinal analgesia. Before the members of the Congress of Surgeons present, I injected into the cauda equina twenty-six minims of a one per cent solution of stovain. The patient, who presented no symptoms differ- ing from those of the average subject during the spinal injection, was then sent to another room to be operated upon by E. M. Foote and Claude A. Frink, of my staff, while I concluded my lecture before the Congress. The man's mind was perfectly clear, his pulse was good, there was no nausea, no cyanosis, no respiratory embarrassment — in fact, none of the symptoms of stovain jmsoning. He suddenly turned pale, said, "I am dying," and instantly died. The case was made a coroner's case, and an autopsy was performed the next day, with the following findings : Marked edema of the brain, so-called "wet brain"; myocarditis; atheroma of aorta; aortic insufficiency; emphysema of lungs; chronic interstitial splenitis ; chronic gastritis ; chronic enteritis ; chronic intersti- tal nephritis. Spinal cord showed no gross lesion. The coroner's inquest was held on December 4, 1912. The jury, after listening to the testimony of the above facts and a number of experts as to the indications of death by stovain poisoning, did not find that the man died of stovain poisoning, but that death was caused "by pathological conditions" as described, and all concerned were exonerated from blame. SPINAL ANALGESIA AND SPINAL ANESTHESIA 627 CONCLUSION In summing up the entire subject of spinal analgesia, the author of this section wishes to reiterate that this method is not to be considered as replacing inhalation anesthesia. It has, however, a distinct place in sur- gery, and as the indications and contraindications are more clearly un- derstood and the technique of the method improved, its field of useful- ness has widened, and will doubtless continue to widen. It must never- theless still occupy a limited sphere until further accurate and scientific experimentation has led to more certain conclusions with reference to the physiological action of the agents employed and the dosage in which they may be used to obtain a given result. CHAPTEE XVI ELECTEIC ANALGESIA, SLEEP, AND EESUSCITATION Louise G. Eobinovitch, B. es L., M. D. (Paris) History: Electric Source and Technique; Application in Man; Contraixidications ; Electric Analgesia and Sleep in Wireless Circuits; Conclusions. Electric Analgesia and Electric Eesuscitation After Heart Failure Under Chloroform or Electrocution : Exclusion of the Head; Kind of Current Used; Procedure; Limitations; Application in Accidental Electrocution; Application in Surgery; Clinical Applica- tions. History. — In 1890 d'Arsonval found that high frequency currents above 3,500 and not over 10,000 periods per second caused a certain degree of anesthesia. In 1892, or earlier, Hutchinson found that induction currents, frequently interrupted with the ribbon vibrator that he had invented, caused anesthesia.^ In 1901 Mile Pompilian produced anes- thesia in frogs by subjecting them to induction currents frequently interrupted by means of a revolving wheel with 12 insulated segments designed by herself.^ In 1902 Leduc and Eouxeau experimented with direct currents interrupted by means of a revolving wheel designed by them. This wheel had 4 insulated segments.^ There were 2 contact levers; one lever was fixed and the other adjustable. By changing the relative position of the movable level it was possible to change the period of the passage of the current. One-tenth of the entire period during a revolution was found to be the most favorable condition for producing what was then called electric "sleep" or "anesthesia." In 1905 we found, while working in the laboratories of these two pro- fessors, that an induction current obtained by an induction apparatus in which the primary coil was run by means of a frequently interrupted di- rect current, 6,000 times per minute, period 1/10, produced deep anesthe- ^ Verbal information given by the New York manufacturers of coils with the ribbon vibrator. ^ Personal communication. ^ Rouxeau did not know of the existence of Mile Pompilian 's models when he designed his wheel. 628 ELECTRIC ANALGESIA, SLEEP, AND RESUSCITATION 629 sia in rabbits. While working out the details of the physiology of electric "anesthesia" we pointed out the dangers of using induction currents on animals,^ especially when the head was included in the circuit. In 1900 researches into the blood pressure, temperature, respiration, and duration of electric "sleep," as well as studies of the effects of the two polarities and of various electric currents, were conducted. In 1907-1908 we per- fected the interrupter, general instrumentation, and technique of appli- cation. ^ In 1909 we pointed out that a certain degree of analgesia and sleep could be obtained in rabbits with currents generated by a Vreeland oscillator, the preferred form of current being a pulsating one.^ In December, 1909, we found that "sleep" could be produced by uni- polar and even by wireless methods in paths of displacement currents. In 1910 we obtained myogram traces showing muscle-nerve reaction in paths of displacement currents by both the unipolar and wireless method. After we had registered these myogram traces. Law found a valuable reference to Danilevsky's remarkable experiments on muscle-nerve reaction in the vicinity of powerful electromagnetic fields.* The first physiological investigations on electric sleep, or anesthesia, were made by Rouxeau.^ The detailed physiologic researches into this sleep and anesthesia were made by us in his laboratory. Utilization of this anesthesia in laboratory surgery was made in 1906. To eliminate the muscular rigidity caused by the earlier models of interrupter, we per- fected the wheel interrupter and pointed out the danger of using the city current, alternating, rectified, ordinary wet battery, and all sorts of ir- regular currents.^ In 1907 we employed electric sleep and anesthesia in clinical work,'^ and electric analgesia was applied by us locally in 1910. ^ Eobinovitch : ' ' Sommeil electrique, epilepsie electrique et electrocution, ' ' These, Paris, 1906. ^Kobino witch: "Electric Anesthesia or Sleep," HandbooJc of Med. Sci., N. Y., 1907; "Electric Anesthesia; Its Use in Laboratory Work," J. Kent. Path., 1907, No. 3. * Eobinovitch : "Physiologic Effects of a New Variety of Electric Current," J. Ment. Path., 1909, No. 4; also, Med. Bee, Dec. 11, 1909, 1009. -^ * Danilevsky : ' ' De 1 'excitation des nerf s par les rayons electriques, ' ' Compt. rendu du XXIIeme Cong. Inter, de Med., Moscow, Aug., 1847, 59. ^ Leduc and Eouxeau : ' ' Du temps pendant lequel peut-etre maintenu 1 'etat du sommeil electrique," Compt. rend. d. I. Soc. d. Biol., July 4, 1903; also, "De 1 'influence du rhythme et de la periods sur la, production de 1 'inhibition par les courants intermittents de basse tension." ® Eobinovitch : ' ' Electric Anesthesia, Its Use in Laboratory Work, ' ' J. Ment. Path., 1907, No. 3; also, "Anesthesie electrique; application elinique; pre- sentation de malades et d 'instruments, ' ' Bull. d. I. Soc. Clinique d. Med. ment., Nov., 1908, No. 4; also, "Motor-interrupter Supplying a Current of Frequent Interruption for Electric Anesthesia," Bull. d. I. Soc. Clinique d. Med. ment., Nov., 1908. ' Eobinovitch : * ' Electric Anesthesia in Laboratory Surgery Successfully Ap- plied During a Period of Three Years. Demonstration on an Animal and Clinical 630 ANESTHESIA Electric Source and Technique. — Pending further investigation of our findings and practical application of wireless electricity for producing sleep in man, we shall go over the matter, dealing with currents in wired circuits in relation to sleep and analgesia, as we have applied it in clinical work as well as in animal and in human surgery. Nothing but storage batteries of large capacity, 100 to 200 amperes, should be used.^ The current used for the patient and the motor should come from two separate sources. The current to be used for the patient is connected with the inlet binding posts of a graphite rheostat. A wire po- tentiometer should not be used because it brings troublesome inductance into the circuit, as is explained in Figures 265, 266, 267, and 268. The current is interrupted on the negative pole ; this pole is connected as follows : a wire connects the outlet binding post of the potentiometer (negative pole) with the wheel interrupter, a milliamperemeter, a switch, and finally a resistance box (Wheatstone bridge or any graded resist- ance). The other binding post of the potentiometer (positive) is con- nected directly with the bridge. The resistance put into the circuit is from 300 to 500 ohms. The resistance represents the patient or the ani- mal. The circuit is then closed by means of the switch. A voltmeter is connected in shunt; all the other instruments are in series. The wheel interrupter is put in such a position as to allow the passage of the direct current without interrupting it (the wheel is not revolving). The volt- meter indicates, say, 40 volts; the milliamperemeter indicates, say, 20 milliamperes. Now the wheel interrupter is made to revolve by means of the motor, say, 1,500 to 2,000 times per minute. Whatever the amper- age is while the wheel is interrupting the direct current, it is the aim to regulate the period of the passage of the current so as to have it pass only 1/10 of the time, 9/10 being lost. This is accomplished by changing the position of the adjustable contact lever in relation to the fixed lever on the wheel, while the latter is revolving. Keep on adjusting the movable lever until the milliamperemeter that registered 20 milliamperes when the wheel was stationary now registers only 2 milliamperes while it is re- volving. The period of the passage of the current is now 1/10. It is of the utmost importance in this work and should be regulated every time Application, Presentation of Patients," J. Ment. Path., 1909, No. 4; also, "Pres- entation of Instmments: Motor-interrupter Supplying a Current of Frequent Interruption for Electric Anesthesia, ' ' J. Ment. Path., 1909, 8, No. 4. ^ Robinovitch : ' ' Electric Anesthesia, Its Use in Laboratory Work, ' ' J. Ment. Path., 1907, No. 3 ; also, ' ' Anesthesie electrique ; application clinique ; pres- entation de malades et d 'instruments, " B^lll. d. I. Soc. Clinique d. Med. ment., Nov., 1908, No. 4; also, "Motor-interrupter Supplying a Current of Frequent Interruption for Electric Anesthesia," Bull. d. I. Soc. Clinique d. Med. ment., Nov., 1908. Fig. 265. — Myogram No. 5. Unipolar Method. Reaction at make and break of direct- current feeding field coils. At break of current reaction is more marked than at make. M, make; B, break. Fig. 266. — Myogram No. 6. Reactions at make of direct-current feeding field coils, at make of arc and at break of direct-current feeding field coils and vacuum tube. M, make; A, arc; B, break. Fig. 267. — Myogram No. 7. Upper tracing; wireless; one end of wire connected with binding post of damp chamber. Other end of this wire held at a distance of fifteen centimeters from field coils and arc in vacuum tube; these coils and arc in vacuum tube in operation. No weight on muscle. Lower tracing: end of the wire three cen- timeters from tube anode. Reactions take place at make and break of arc in vacuum tube. Fig. 268. — Myogram No. 8. Lower tracing: primary coU only; "wired" circuit with "gap" of five centimeters. M, reaction as soon as ribbon vibrator is in operation and magnetic flux brought into play. T, reaction while operator was touching base of stand holding muscle-nerve preparation. Rest of trace, spontaneous irregularity, while free end of wire was held in magnetic flux. Upper tracing: with a circuit "gap" of five centimeters and end of wire held near magnetic fiux. No reaction when wires withdrawn from field. 632 ANESTHESIA before an experiment is commenced.^ Now reduce the current to zero with the potentiometer, break the circuit by opening the switch, take out the bridge and substitute for it an animal or a patient. The wheel is Fig. 269. — Myogram No. 9, "Unipolar." Primary coil only (10 inches long, six layers of wire, of which diameter is ^f mm., condenser in circuit. Core one inch in diameter. No weight on muscle) ; reaction when one end of the single wire is connected with damp chamber, the other end touching any part of the metal frame near magnetic flux. M, reaction when end of wire touches any part of metal frame; T, operator touch- ing with hand base of drum on which trace is registered; S, operator touching base of stand holding muscle-nerve preparation. made so that it can interrupt the current from 6,000 to 12,000 times per minute, according to the speed of its rotation. It is dangerous to use any other current than that indicated above. Alternating, induction, rectified currents, or those supplied by ordinary Fig. 270. — Myogram No. 10. "Wireless." No weight on muscle. From below upward ; lowest line; Tesla high frequency. Preparation grounded; no spark across Tesla ter- minal apparatus one foot away from preparation. The two upper traces: oscilla- tions conducted to preparation by operators' body, as explained in the text. Spark across Tesla terminals. wet batteries are dangerous for this work. Irregular direct currents are equally dangerous. Bad results may be obtained in experiments in ani- mal surgery by irregular currents, when laundries and elevators are run by power taken from the same main line as that supplying the labora- tories. Unsuitable apparatus combined with such markedly uneven cur- rents accounts for death and convulsions in animals, especially when too ^ A firm in New York has constructed, under our direction, an interrupter with a fixed period of the passage of the current. ELECTRIC ANALGESIA, SLEEP, AND RESUSCITATION 633 hio-h amperage is used. Correct technical construction of the apparatus is of utmost importance. When used with a wire potentiometer in the circuit, even our best model of interrupter caused muscular rigidity because of inductance. The myograms fully explain the difficulty. We have found that sul)stitution of a graphite rheostat for one made of wire eliminates this difficulty to a large extent. Application in Man, — For Inducing Sleep. — Leduc was the first to submit himself to electric "sleep." Eouxeau and Malherbc applied the Fig. 271. — Myogram No. 11. "Wireless." Weight on muscle. From above down- ward: 1, reaction at a distance of 2 meters; each end of solenoid screwed into respective binding posts on disc of damp chamber; 2, reaction at a distance of 2 meters, one end of solenoid being free in the air; 3, reaction at a distance of 23^^ meters, solenoid with one free end in the air reinforced. current; the experiment was not pushed far enough to produce complete anesthesia; 35 volts and 4 milliamperes were used centrally. In our work we distinguish between electric sleep and analgesia. We produce electric sleep in patients suffering from insomnia by applying to the forehead, the negative electrode shaped to the forehead and the posi- tive electrode to the palm of the right hand. The current is turned on slowly, generally, some 5 minutes being consumed in turning on % of a milliampere. When this amount of current is reached, the patient feels a tingling sensation through his head and falls asleep within a few minutes. A small flag mounted on a little block of wood is placed upon the patient's chest ; the flag moves with the movements of the chest, that are watched all the time while tlie patient is slee]3ing. We generally allow the current to course through the body for 1 hour, then turn it off; but the patient continues to sleep. On awakening the patient feels re- freshed ; if he is very sensitive, he may remark that he feels "a bit chilly." This chilly feeling is probably caused by the vasoconstriction during the passage of the current. 634 ANESTHESIA For Local Purposes. — In clinical work we have applied electric anes- thesia in numerous cases. The chosen part of the body or limb is in- cluded in the circuit, the cathode always being nearer the central nerv- ous system, the anode being the distal electrode. If the chest is in the circuit the amperage should be governed judiciously. For Surgical Purposes. — We applied local electric analgesia in man for surgical purposes in 1910; the patient, a man twenty-three years old, was at the St. Francis Hospital, Hartford, Conn. M. M. Johnson, assisted by Edward Herr, operated. The patient talked with those near him while his toes were being amputated. The great toe of one foot and the great, second and third toes of the other were ampu- tated. The operation was "bloodless." Four milliamperes of current and 54 volts were used in this case. Other surgical cases in which we applied electric analgesia locally are not yet published. One of these was a major operation of the lower limb and was also "bloodless." The vasoconstriction accounts for the insignificant loss of blood. In some cases we used 9 milliamperes for amputation of the toes (one in a man, another in a woman) and 18 milliamperes for resection of the leg in a man. Neither one of these patients withdrew the limbs during the operation, although the surgeons urged them to do so if they felt pain. They only complained of the tingling sensation caused by these strong currents. We believe, therefore, that 4 milliamperes of current, applied with electrodes of the dimensions reported by Johnson, are most favorable. Local analgesia depends entirely on proper technique in the applica- tion of the electrodes. In the lower extremities application of the elec- trodes is quite easy, because the anterior crural nerve and its accompany- ing vessels in Scarpa's triangle are readily reached with an electrode; so are the anterior and posterior tibial nerves in the leg. In the upper extremities it is rather difficult to hold the electrode applied over the large trunks of nerves and vessels. When the electrodes are properly applied to them the analgesia is good ; but it is difficult to keep the elec- trodes in their proper places. Locally, the amperage may readily be increased above 4 milliam- peres; we do not recommend higher amperage than 4 milliamperes of the interrupted current; but 5 or 6 milliamperes may sometimes be necessary. Centrally, 4 milliamperes is as strong a current as should be applied. Currents slightly stronger than this should be used by none but the expert in this work. The major advantage of this analgesia is that it is not dangerous when properly applied, with proper instruments and proper currents.^ ^ This is part of a paper, ' ' Electric Anesthesia and Electric Eesuscitation After Heart Failure under Chloroform or Electrocution. ' ' Eead in the Section of ELECTRIC ANALGESIA, SLEEP, AND RESUSCITATION 635 Contraindications. — Electric sleep, and particularly analgesia, when applied centrally, causes abortion in pregnant animals. The cur- rent is contraindicated in cases of high arterial pressure, in the apoplectic and in the epileptic, because this current increases arterial tension. Electric sleep or analgesia should not be combined with morphini- zation, chloroforming, or soporific agents.^ Electric Analgesia and Sleep in Wireless Circuits.^ — In 1909 a new variety of electric current was used — one produced by a Vreeland oscil- lator.* Babbits and dogs were subjected to the effects of this current and a certain degree of analgesia and sleep was produced. In one rabbit the tissues of the back of the chest were even cut through and the bones of the spinal column scraped with a knife, without causing any apparent reaction to pain. But in dogs we could not produce any analgesia for operative purposes without using a current so strong that it caused excessive muscular rigidity and endangered life. The more interesting feature of the effects of this pulsating current was in regard to sleep. A dog was put into a closed wired circuit of this current. The animal remained stretched out on its side, in a condition of muscular relaxation, during a period of 3 hours, when one of the electrodes accidentally be- came disconnected. The animal, however, continued in a condition of somnolence for 14 hour thereafter, despite the continued disconnection of one electrode in this circuit. A pin was thrust through its skin and the animal arose to its feet. We repeated similar experiments of uni- polar connection with the working current of the oscillator, and similar results were obtained. We then disconnected both electrodes, and still the dog remained on its side in a drowsy condition upon the table, awaking only when shaken vigorously. While the animal remained in a drowsy condition the oscillator was in operation. The oscillator's important features in relation to this sleep were not the working current supplied by the apparatus, this cur- rent not being used then, but the two field coils and rapid electric oscil- lations in the vacuum tube of the apparatus made for the purpose of supplying the working current. The magnetic flux and the arc in the Pathology and Physiology of the American Medical Association, St. Louis, Mo., June, 1910. ^Robinovitch: "Electric Anesthesia in Laboratory Surgery Successfully Ap- plied During a Period of Three Years. Demonstration on an Animal and Clinical Application, Presentation of Patients," J. Ment. Path., 1909, No. 4; also, "Pres- entation of Instruments: Motor-interrupter Supplying a Current of Frequent Interruption for Electric Anesthesia," J. Ment. Path., 1909, 8, No. 4. ^Med. Bee, Dec, 1910. * Robinovitch : "Physiological Effects of a New Variety of Electric Cur- rent," J. Ment. Path., 1909, 8, No. 4; Med. Bee, Dec. 11, 1909, 1009. 636 ANESTHESIA vacuum tube caused displacement currents in the air, as is shown in the myogram studies. In our experiments the continuance of electric sleep in dogs by- means of displacement currents was practised after the animals had been subjected to the effects of the pulsating current conducted through a closed wired circuit during periods of from 2 to 3 hours. We are not in a position to affirm that this sleep could be obtained in all dogs without the preliminary effect of the pulsating current in a wired circuit. But myograms obtained demonstrate the decided effect of displacement cur- rents on living tissues; these studies seem to indicate that, where we failed to produce sleep with displacement currents at our disposal, it was because these currents were not sufficiently strong for the purpose. In these experiments the muscle-nerve preparation is in a damp chamber, covered with a glass globe; the nerve lies across two non- polarizable electrodes ; these electrodes are filled with a saturated solution of zinc sulphate, and wires connect them with binding posts on the disk of the damp chamber. Conclusions. — Living beings and muscle-nerve preparations react to displacement currents. A muscle-nerve preparation may react to cur- rents that an ordinary telephone receiver does not detect. A muscle- nerve preparation seems to be a sensitive detector of displacement cur- rents. An electromagnetic flux of an ordinary portable small-sized primary coil with a ribbon vibrator in operation causes muscle-nerve reaction in circuits with gaps of from 3 to 5 centimeters. A larger electromagnetic flux (core 10 inches long, 1 inch in diameter, primary coil six layers of wire, diameter 12/10 mm., with condenser on primary) causes marked reaction by unipolar methods. It is possible to produce effects on ani- mal and living tissue by means of unipolar and wireless methods. The question of producing sleep in man in paths of displacement currents requires further study. In our studies of wireless effects of displacement currents on living tissue, positive results have also been obtained without grounding the muscle-nerve preparations and even when everything connected with the experiment was insulated on a platform. This proved that reactions could be obtained by reason of free displacement currents in the air.^ Electric Analgesia, and Electric Resuscitation after Heart Failure "Under Chloroform or Electrocution.^ — By the use of electric currents it is possible to resuscitate subjects in a condition of apparent death caused ^Med. Bee., Aug. 13, 1910. = " Electric Anesthesia and Electric Eesuscitation After Heart Failure under Chloroform or Electrocution." Am. Med. Assn., June, 1910. The part on resus- citation was published in the J. Am. Med. Assn., Feb, 18, 1911, 56, 478-481. ELECTRIC ANALGESIA. SLEEP, AND RESUSCITATION 637 by chloroform, ether, morphin, electrocution, etc. The first important researches into resuscitation of electrocuted subjects were made at about the same time by Battelli ^ in Europe and H. H. Cunningham in this country.^ Both authors used enormous currents for causing single elec- tric shocks with which they attempted to restore life after ventricular tremulation had set in. Battelli used 4,800 and 2,400 volts respectively, of alternating currents (amperage not stated). The means was not practical because one shock caused with such high voltage was all the heart could stand; a second shock killed the animal definitely. Leduc and Eouxeau ^ tried to resuscitate animals by means of direct interrupted currents of low tension, but they committed their prede- cessors' error of including the animal's head in the circuit. Besides, they used the lethal current for producing the shocks. The method was use- less in cases of dogs. Exclusion of the Head. — While experimenting on the cerebral circu- lation during electric epilepsy,* we saw, through a trephined opening in the skull, that every electric shock caused profound anemia of the brain at the time of the closure of the circuit. This led us to exclude the ani- mal's head from the circuit during the rhythmic excitations, in order to exclude the medulla oblongata with the cardiac and respiratory cen- ters, and to avoid any further anemia of these centers during apparent death, while the electric rhythmic excitations were being practiced. We also reduced the current to minimal doses for the first rhythmic excita- tions, because we found that useful cardiac and respiratory excitability was rapidly exhausted within the few minutes of apparent death. The maximum potential at the end of the resuscitation did not exceed 120 volts. Even this is too high voltage: in dogs it causes marked vagus stimulation, so that the heart beats are very slow during a long period of time after resuscitation, and the wave form of the beat does not re- semble the normal form. In ordinarily severe cases, 70 volts is a good maximum potential.^ ^ Battelli and Prevost: "La mort par les courants electriques: courant alternatif a bas voltage et a haute tension, "J. d. Physiol, et de Path, gen., May, 1899. -Cunningham: "The Cause of Death from Industrial Electric Currents," N. Y. Med. J., 1899, 70. ^Quoted by Eobinovitch, in "Sommeil electrique, epilepsia electrique et electrocution," These, Paris, 1906. * Eobinovitch : "General and Cerebral Blood Pressure During an Attack of Electric Epilepsy," J. Ment. Pathol, 1907, 8, No. 3. ° Eobinovitch : ' ' Method of Eesuscitating Animals in a Condition of Cardiac and Eespiratory Syncope Caused by Chloroform," J. Merit. Path., 1907, 8, No. 3. "Method of Eesuscitating Electrocuted Animals," ibid.; "Method de rappeller a la vie des animaux en syncope cUorofomiique et des animaux en mort ap- parente causee par 1 'electrocution. Effets differents de differents courants elec- triques. Importance d 'exclusion du circuit electrique de la tete de 1 'animal 638 ANESTHESIA The method of resuscitation consists in causing artificial blood pres- sure and respirations by means of rhythmic electric excitations, until normal function is restored. Kind of Current Used. — Our choice of electric current is the one we use for causing electric sleep and analgesia : a direct current, interrupted from 6,000 to 8,000 times per minute, period 1/10. Next in value is a direct current interrupted from 25,000 to 40,000 times per minute with a triple interrupter.^ The last choice, and the one that we do not rec- ommend if the first two can be had, is an induction current obtained with our special model of induction coil, an ordinary Dubois-Reymond coil, the special feature of which is the diameter of the wire of the coil, 1.2 mm. for the primary and 0.6 mm. for the secondary coil.^ In cases of grafve forms of apparent death, currents supplied by coils with fine wire will kill the animal.^ Induction currents are alternating currents, the wave form of the current running above and below the base line. The physiologic effects of anodal and cathodal stimulations are distinctly dif- ferent; the anodal stimulations are particularly dangerous in pulmonary and cardiac areas when the current is obtained from a secondary coil the wire of which is finer than 0.6 mm. Alternating and direct currents are deadly to cellular life, especially during apparent death.* But, if noth- ing else can be had, rhythmic excitations may be practiced with these currents, rather than make no attempt to save life. Procedure. — The dog's back is shaved in two places — on the chest covering the pulmonary area and the back over the loins. The negative electrode is applied under the chest, the upper border reaching to the root of the neck. It is dangerous to use the positive pole under the chest. The positive electrode is applied over the loins. The electrodes measure 12 by 25 cm. for dogs of large size. They are made of zinc and are cov- ered with a thick layer of absorbent cotton wet in a salt solution, 7 : 1000. In man the chest electrode measures 25 by 30 cm. Chloroforming is performed intensively, admitting little or no air pendant les excitations rythmiques, " Compt. rend. Soc. de Biol., Feb. 1, 1908; "De I'emploi des courants electriques pour le rappel a la vie, dans les cas de mort apparente causee par le chloroforme ou par 1 'electrocution. Necessite d 'exclure du circuit la tete, pendant les excitations rythmiques. Experiences pratiquees sur le chien. Application clinique, ' ' Bull. Soc. Clin, de Med. ment., Nov., 1908; "Resuscitation of Subjects in a Condition of Apparent Death," etc., J. Ment. Path., 1909, 8, No. 4. * Robinovitch : "Triple Interrupter of Direct Currents for Resuscitation. Portable Model for Ambulance Service, ' ' J. Ment. Path., 1909, 8, No. 4. ^ Robinovitch : ' ' Bobine a induction pour rappel a la vie, etc., ' ' Bull. Soc. Clin. d. Med. ment., Nov., 1908 ; ' ' Induction Coil for Purposes of Resuscitation, ' ' J. Ment. Path., 1909, 8, No. 4. * Robinovitch : Thesis, loc. cit. * Robinovitch : "Different Effects of Various Electric Currents for Pur- poses of Resuscitation, etc. ' ' J. Ment. Path., 1909, 8, No. 4. ELECTRIC ANALGESIA, SLEEP, AND RESUSCITATION 639 and causing arrest of respiration and heart beats as quickly as possible. When breathing is no longer registered by the pneumograph and the manometer does not register any blood pressure, the chloroforming is discontinued at once. An assistant holds the animal's tongue with a tongue forceps, cleanses the mouth of mucus, and pulls the tongue out- ward to allow free access of air during the rhythmic excitations. The instrumentation with the preferred current is the same as that used for electric sleep. The operator now opens the switch of the cathode line and turns on a current of some 20 to 25 volts by means of the potentiometer. The circuit is then closed by means of the switch for a fraction of a second. A deep inspiratory movement takes place. The mouth opens, the flabby, lifeless tongue that was lying on the roof of the mouth (the animal is on its back) contracts and is drawn inward; the fore paws are thrust upward with marked force; the posterior limbs are extended; the diaphragm is pushed downward and all the respira- tory muscles enter into play. The chest is fully expanded and the pneu- mograph registers an ample artificial inspiration. The manometer may also register an artificial blood pressure; but in cases of severe car- diac syncope the first few rhythmic excitations cause respiratory reaction without artificial blood pressure. The operator breaks the circuit by opening the switch. This is followed by a deep expiratory movement, and all the muscles that entered into play to cause the artificial inspiration are now again fiabby and lifeless; the expanded chest collapses and the pneumograph registers an ample expiration; the anterior paws fall one on each side of the body, the tongue falls to the roof of the mouth, life- less, the mouth closes and the whole body is again lifeless and relaxed. The switch is kept open for a period of from % to 1 second, according to the gravity of the case. If the first voltage used causes an ample respiratory reaction and the manometer shows a momentary rise of blood pressure, the succeeding rhythmic excitation is caused with the same voltage, but, as a general rule, it is necessary to increase the cur- rent to 30 volts or more; the excitations are now practiced with the in- creased current, the aim being to obtain ample respiratory reaction and blood pressure with this minimal voltage within the shortest possible time, because useful cardiac excitability is quickly exhausted during apparent death. It is generally necessary to increase the current to 35, 40, 50, 60, and 70 volts within the course of 3 or more minutes of ap- parent death; the excitations are being practiced while the voltage is being increased. In favorable cases ample respiratory reaction and ar- tificial blood pressure are soon established, then accompanied by feeble spontaneous respiratory and cardiac reactions; these soon increase in amplitude; they are alternated with ample artificial reactions if neces- sary, taking care not to encroach on the spontaneous heart beats and respirations, but rather to precede or to follow them. The operator Fig. 272. — Tracing No. 1. Made During Usual Form op Apparent Death Caused BY Intensive Chloroforming in a Dog. Upper tracing, respiration; second tracing, blood-pressure in carotid artery; third tracing, time; two lines indicate one second, during cardiac failure only. In rest of tracing: one line indicates one second. R, respiratory syncope; C, cardiac syncope; E, commencement of electric rhythmic excita- tions (direct current interrupted 8,000 times per minute, period 1-10) ; gradual in- creasing current from 20 to 65 volts. The ample respiratory and cardiac reactions are artificial, caused by the rhythmic excitations; then the small spontaneous heart-beats appear and alternate with the ample artificial ones. The cross shows where the first small spontaneous respiration appeared ; ample artificial respirations alternate with the small spontaneous ones. S, synchronous respirations and heart-beats; final resuscita- tion. 1 0/i ,^^ ^^^,^T-,^.'-rt^,-,.^rf-,Ttvn>'^rtU^i+*»iJli-'*^-. — 1-^ — 'y^'^\. ' X, /\m'mt^""- B^BB Fig. 273. — Tracing No. 2. Primary Cardiac Syncope in Dog. Intensive chloroform- ing. Upper line, respiration; second line, blood pressure in carotid artery; third line, signal; fourth line, time, one second. Tracing reduced one-half. Imitation of method used by surgeons (Sylvester method) : small respiratory reaction caused by limited current of 8 volts (6,000 interruptions per minute, period 1-10). S, cardiac syncope, respirations continuing; R, rhythmic excitations; C, commencement of spontaneous cardiac beats; D, spontaneous respiration does not appear; commencement of descent of blood pressure, ending in death of animal. ELECTRIC ANALGESIA, SLEEP, AND RESUSCITATION 641 Judges by the spontaneous cardiac and respiratory reactions when it is ad- visable to discontinue the rhythmic excitations. If they are discontinued too soon, death may set in -after resuscitation, because iji chloroform poi- soning the blood is asphyxiated and dark; the feeble respirations and heart beats may not be sufficient to cause useful oxygenation of tlie blood. But once ample spontaneous reactions are established, the carotid artery is tied, the wound is closed, and the animal lives without showing any ill effects. We have kept such dogs during a period of one year and longer after resuscitation; they were in excellent condition. :U)iiliii(:i| v^^.**Jir'w,wM*i^*iitMv.-'Wi.^^^^^^ Fig. 274. — Tracing No. 3. Primary Cardiac Syncope in Dog. Intensive chloroforming. Upper line, respiration; second line, blood pressure in carotid artery; third line, signal; fourth line, time, one second. Tracing reduced one-half. S, cardiac syncope, respira- tion continuing ; E, commencement of the rhythmic excitations with induction current, wire of secondary coil 6-10 mm. in diameter; gradually increasing current causes gradually increasing amplitude of artificial respirations; C, commencement of ample artificial heart beats; small heart beats are spontaneous and alternate with artificial ones; R, spontaneous respirations and final recovery. Limitations.^ — The period of apparent death is short; four minutes (including the time of the rhythmic excitations) is a long time, and 5 minutes is an exceedingly long period. But, once resuscitated, the ani- mal lives and shows no after-effects. In chloroform poisoning death may take place in various ways : By respiratory arrest and ensuing cardiac failure, which is the usual form in man; by primary cardiac failure, which is a rare form in dogs, but is quite familiar to surgeons in the case of human beings ; and by simul- taneous cardiac and respiratory arrest. In the majority of cases, in human beings as well as in dogs, death sets in by respiratory paralysis followed by cardiac failure. Figure 272 shows the usual form of apparent death from chloro- form poisoning and the mode of resuscitation by electric rhythmic ex- citations with a gradually increasing current. The amperage cannot be read in these experiments because the closures are of too short duration, but there are generally between 4 and 40 milliamperes of current used. 642 ANESTHESIA This amperage was obtained in experiments on dogs sacrificed for this purpose. Figure 273 shows primary cardiac syncope in a dog during chloro- forming; imitation of the Sylvester method of resuscitation: feeble current causing the delayed and feeble cardiac and respiratory reaction that ends in death. Figure 374 shows primary cardiac syncope in a dog during chloro- forming; resuscitation was practiced by gradually increasing the cur- rent. The result was recovery. Electrocuted dogs are resuscitated less easily than are chloroformed dogs. It is especially difficult to resuscitate when ventricular tremulation sets in. All experimenters on this subject agree that artificial respiration and the Sylvester method are useless when ventricular tremulation sets in.^ Our method seems to give the best results known to-day for prac- tical application, because it produces ample artificial blood pressure as well as respiration. Application in Accidental Electrocution. — According to personal information given us by practical electricians both in Europe and this country, death does not always take place instantaneously in accidental electrocution with moderate industrial currents. The workingman gen- erally touches the "live" wire with his hand or foot ; contact is generally "bad/' but it is sufficient to cause cardiac and respiratory paresis, from which the patient may die within from a few minutes to one-half hour after the accident. These are facts observed in daily accidents, regard- less of some experimenters' claim that all is well if the patient's heart beats and he breathes when taken out of the circuit. The blood is asphyxiated and dark, after the slightest shock; a few rhythmic electric excitations will help to whip up the circulation and respiration, if the excitations are practiced immediately following the accident or as soon as possible — before the patient is removed to a hos- pital. Without this help, the patient may die when he is brought into the ward — some half hour after the accident. The blood remains as- phyxiated even after resuscitation. This asphyxia may continue during many hours. Application in Surgery. — Direct and indirect cardiac massage has claimed its victims of chloroform poisoning in surgical work.^ Crile's method of resuscitation is admirable as regards the range of time dur- ing which the heart's action may be restored. Unfortunately, it pre- sents physiologic limitations ; attempted resuscitation after a period of 7 minutes (in man), counting from the time of cardiac arrest, becomes * Eodenwaldfc, Ernest : ' ' Ueber Verletzungen durch elektrische Starkstroeme vomgerichtsaerzlichen Standpunkte, " Vrtljschr. f. gericht. Med. (3), 37, 1. - White, Charles S. : " The Kole of Heart Massage in Surgery, ' ' J. Surg. Gynec. and Obstet., Oct., 1909. ELECTRIC ANALGESIA, SLEEP, AND RESUSCITATION 643 useless, because the anemia of the brain during this time is fatal to the life of the brain cells; the restoring of heart action becomes useless from the point of view of restoration of life. The method has the great advantage of simpli(;ity ; it does not neces- sitate opening the carotid artery and injecting a pint or so of solutions into the heart ; it does not necessitate opening the trachea. The method may be applied immediately when the first sign of cardiac or respiratory failure appears. Before an operation is commenced the electrodes may be put in their proper places under the patient; the chest electrode, 25 by 30 cm., the loin electrode, 12 by 25 cm. The apparatus and chosen elec- tric source should be in readiness before the operation is commenced. The tracing shows that it is possible to resuscitate dogs after respira- tory and cardiac functions are no longer registered during a given period of time. It should not be assumed, however, that resuscitation is easy in all grave cases. There are no two subjects alike in physical vitality. For practical application in surgery the safest method is to commence rhyth- mic electric excitations at the first sign of respiratory or cardiac failure. The surgeon does not wait until both the respiration and the heart have failed. In a series of experiments on dogs we commenced the rhythmic excitations a few seconds after respiratory syncope set in — in imitation of what a surgeon would do if he had a patient showing signs of syncope caused by chloroform or ether. Resuscitation was easy and complete in these experiments after a few rhythmic excitations. Eesuscitation is more difficult, of course, when heart failure dominates in the accident. Considered in its proper light, the method should really serve as a preventive measure against grave forms of syncope, because a few rhyth- mic excitations, practiced in time, promptly oxygenate the blood by reason of the ample respiratory and cardiac reactions. Clinical Application. — In November, 1908, we had occasion to revive a patient in a condition of profound syncope caused by chronic morphin poisoning. She was in Magnan's service, Ste. Anne Asylum, Paris. Magnan had revived her after she had had a first attack of syncope. A second attack set in within a few minutes; his assistants attempted to revive her by applying the Sylvester method and rhythmic traction of the tongue; this proved useless during a period of 20 minutes. The pa- tient's face became "blue" from asphyxia. As is known, in morphin poisoning the respiratory center is paralyzed first, and heart failure fol- lows, as is the case in ordinary asphyxia. The patient's respirations were about 3 or 4 per minute; the pulse was hardly perceptible, and death seemed to be imminent. We applied electric rhythmic excitations; the patient revived defi- nitely after a period of from 25 to 30 seconds.^ ^ Eobinovitch : "Eesuscitation of a Woman in Profound Syncope Caused by- Chronic Morphin Poisoning," J. Ment. Path., 1909, 8, No. 4. CHAPTER XVII MENTAL INFLUENCE AND HYPNOSIS IN ANESTHESIA PAET I MENTAL INFLUENCE IN ANESTHESIA James J. Walsh, M.D. Hypnotism : Anesthesia in Hypnotic States ; Chemical Anesthetics and Hypnotism; Advantages of Hypnotism in Anesthesia; Hypnotism and Child-birtli ; Hypnotism in Minor Operations; Disadvantages of Hypnotism; Charlatanism and Hypnotism. Suggestion : Suggestion Instead of Hypnotism ; Psj'chic Influ- ences and Surgical Anesthesia; Local Anesthesia and Mental Influence; Mental Influence as a Valuable Auxiliary; Deep Breathing and Concen- tration of Mind ; Preliminary Medication and Mental Influence. HYPNOTISM Anesthesia in Hypnotic States. — When hypnotism developed in the first half of the nineteenth century, its influence on the production of insensibility to pain was noted, and attempts were made to employ it to lessen the awful tortures of surgical operations in the pre-anesthetic days. About 1840 some cases of surgical anesthesia by hypnotism were reported, and there was a discussion on the subject before the Medico- Chirurgical Society of London. In 1843 Elliottson wrote a work well known to persons interested in the influence of mind on body, entitled "Numerous Cases of Surgical Operations Without Pain in the Mesmeric State." Elliottson's treatise, however, attracted very little attention in England. There was profound distrust of procedures of this kind, which had been thoroughly discredited by Mesmer a little earlier in the cen- tury, and which, at that time, were usually called Mesmerism. By 1846, however, so much had been accomplished that Sir John Eorbes, a thor- oughly conservative English medical authority, wrote in his Review for October: "Indeed, we hesitate not to assert that the testimony is now of so varied and extensive a kind, so strong, and, in a certain proportion 644 MENTAL INFLUENCE IN ANESTHESIA 645 of cases, so seemingly unexceptionable, as to authorize us — nay, hon- estly to compel us — to recommend that an immediate and complete trial of the practice be made in surgical cases." Chemical Anesthetics and Hypnotism. — It was on December 17, 1846, that the news of the employment of ether for anesthetic purposes reached England. On December 18 the discovery was announced in the Medical Gazette. ISTothing can better show how much attention hypnotism for anesthesia had come to occupy than the heading under which the anouncement of ether as an anesthetic was made. It was "Animal Magnetism Superseded." On December 19 Lister operated on a patient under ether, and then all attention was given to that sub- ject. As has been pointed out by Hack Tuke, it was soon seen that many sensory phenomena which had been noted under hypnosis for surgical purposes, such as calling out as if in pain, sensitiveness, moan- ing, wincing as if from tenderness, and the like, were not, as many had supposed them to be when they occurred in Mesmeric patients, proofs of imposture or of inability to control their feelings in spite of their wish to do so, or of suppressed suffering, but only curious psychic mani- festations that might well occur in conjunction with a state of complete painlessness. It is easy to understand, however, how, in the progress of chemical anesthesia and the discovery of chloroform as an anesthetic by Simpson, hypnotism no longer attracted attention. Furthermore, El- liottson unfortunately allowed himself, somewhat as did Luys in Paris, to be deceived by some of his subjects. Later this was discovered, and he was compelled to resign as hospital attendant. Elliottson's work, however, attracted the attention of Esdaile in In- dia, who found, on attempting to lessen pain by means of Elliottson's procedures, that he could actually produce complete analgesia. This led him into a series of observations, from which he discovered that he could perform all sorts of operations on his Hindu patients after pre- liminary hypnotism, without any manifestation of pain, and he suc- ceeded in performing painless operations in many hundreds of cases. He had, of course, a particularly favorable field. His patients were devoted to him and had the greatest confidence in his hypnotic and sur- gical powers. They trusted him absolutely. The Orientals have cer- tain mystical tendencies that predispose them to such concentration of mind as keeps external sensations from annoying them, and they proved especially susceptible to hypnotic suggestions. As a consequence, even the most serious operations — -amputations, the removal of stone from the bladder, and even grave abdominal operations — were performed un- der hypnosis without pain, and without any unfortunate effects. Two hundred recorded operations, consisting of the removal of large tumors weighing from 10 to 103 pounds, are the best evidence of this. Case Illustration. — The description of one of Esdaile's cases as re- 646 ANESTHESIA corded by Bramwell ^ shows how much can be done in this way under favorable conditions. The patient was a peasant suffering from a tumor in the antromaxillare. The tumor had pushed up the orbit of the eye, filled up the nose, passed into the throat, and caused an enlargement of the glands of the neck. In the hypnotic condition the patient permitted one of the most severe and protracted operations in surgery. Esdaile describes the operation as follows : "I put a long knife in at the corner of his mouth, and brought the point out over the cheek bone, dividing the parts between; from this I pushed it through the skin at the inner corner of the eye, and dissected the cheek bone to the nose. The pres- sure of the tumor had caused absorption of the anterior walls of the antrum, and, on pressing my fingers between it and the bone, it burst, and a shocking rush of blood and matter followed. The tumor ex- tended as far as my fingers could reach under the orbit and the cheek bone, and passed into the gullet — having destroyed the bones and parti- tion of the nose. No one touched the man, and I turned his head in any position I desired, without resistance, and there it remained until I wished to move it again; when the blood accumulated, I bent his head forward, and it ran from his mouth as if from a spout. The man never moved nor showed any signs of life, except an occasional indistinct moan; but when I threw back his head, and passed my fingers into his throat to detach the mass in that direction, the stream of blood was directed into his windpipe, and some instinctive effort became necessary for existence; he therefore coughed and leaned forward to get rid of the blood, and I suppose that he then awoke. The operation was finished, and he was laid on the floor to have his face sewed up, and while this was being done he, for the first time, opened his eyes." Bramwell, commenting on the case, says : "The patient afterward informed Esdaile that he did not know he had coughed and was quite unconscious up to the termination of the operation." The dressings were removed 2 days afterward, when it was found that the wounds had healed by first intention. The recovery was satisfactory. Such a mode of anesthesia would seem eminently desirable to those who know how troublesome are operations of this nature upon the face, necessitating, as they do, the continuous administration of the anesthetic, and involv- ing the practical impossibility of securing healing by first intention, be- cause of the manipulation necessary for the administration of the anes- thetic. It is interesting to note that Esdaile's assistant had first tried to hypnotize the patient and had failed. Esdaile succeeded in bringing about profound hypnosis only after half an hour of very patient labor. Other cases not unlike this are reported by Bramwell, and there is a series of well-authenticated cases from Braid and Bramwell. It is evi- ^ ' ' Hypnotism, Its History, Practice and Theory, " by J. Milne Bramwell, London, 1906. MENTAL INFLUENCE IN ANESTHESIA 647 dent that, under certain circumstances and for special patients, hypno- tism may prove a valuable auxiliary, and the thought of its usefulness in this regard should not be put aside as visionary until we have had much more experience. Advantages of Hypnotism in Anesthesia. — Bramwell is an enthusi- ast in the matter, and undoubtedly views the subject much more favora- bly than do many others. It must not be forgotten, however, that in sci- ence negative observations are of little value compared with positive observations. Bramwell has succeeded in securing results ; if others can- not, it may very well be because of lack of confidence in themselves, lack of faith on the part of their patients, defect of technique, and want of persistency. Bramwell has summarized some of the advantages of hypnosis as an anesthetic as follows: (I) When once deep hypnosis with anesthesia has been obtained, it can immediately be reinduced at any time. (3) Ko repetition of any hypnotic process is necessary; the verbal order to go to sleep is sufficient. (3) The hypnotizer's presence is not essential. The patient can be put en rapport with the operator by written order, or by other means previously suggested during hypnosis. (4) No abstinence from food or other preparation is necessary, (5) Nervous apprehension can be removed by suggestion. (6) Hypnosis is pleasant and absolutely devoid of danger. (7) It can be maintained indefinitely and terminated immediately at will. (8) The patient can be placed in any position without risk — an important point in operations on the mouth and throat — and will alter that position at the command of the operator. Gags and other retentive apparatus are unnecessary. (9) Analgesia alone can be suggested, and the patient left sensitive to other impressions — an advantage in throat operations. (10) In labor cases the influence of the voluntary muscles can be increased or diminished by suggestion. (II) There is no tendency to sickness during or after operation — a distinct gain in abdominal cases. (12) Pain after operation or during subsequent dressing can be entirely prevented. (13) The rapidity of the healing process, possibly as the result of the absence of pain, is frequently very marked. Hypnotism and Child-birth. — In a certain number of cases hyp- notism has been used successfully for the relief or even complete sup- pression of pains of child-birth. A number of observers, among whom are Schrenck-lSTotzing and a number of French observers, have reported cases in which even the pains of severe labor were thus relieved. There 648 ANESTHESIA is no doubt that the mind can greatly influence the course of labor. It has often been noted that when a patient has expected a particular physician in whom she has confidence, and for some reason another comes in his stead, the labor, which may have been progressing nor- mally or even rapidly, becomes sluggish or its progress ceases entirely. It has been said that insufficient contractions of the uterus and acces- sory muscles can be stimulated by suggestion, while excessive muscular contractions can be diminished in this way. Fianton has even claimed that he can successfully excite premature labor by suggestion. Un- doubtedly mental influence means much in these cases. Probably the persuasion that a definite time should be the occasion for birth may save a woman from the retention of the child in utero for a month be- yond the normal time, while this delay may be occasioned by a wrong persuasion in the matter. Certainly the use of suggestion to save woman from many of the troubles of the puerperium should not be neglected. Hypnotism in Minor Operations. — Many others have employed hyp- notism for the production of insensibility to pain during minor surgical operations. As we have said, it was overshadowed by the newer anes- thetic methods. Some devotees of hypnotism, however, have continued to practice surgical anesthesia by hypnotic methods. Disadvantages of Hypnotism. — It should be borne in mind that there are many drawbacks to this method of inducing anesthesia. Surgical anesthesia requires deep hypnosis. Only a limited number of indi- viduals, probably not more than one in ten (if that many), can be brought into such deep hypnosis as will allow of cutting operations without pain. This is true particularly if the operations are prolonged. The length of the hypnotic state is not always well under control of the operator. Occasionally patients come out of the hypnotic state during the course of an operation; they are then liable to suffer more than if this method had not been employed and to be somewhat uncontrollable. Besides, there are psychic disadvantages. Occasionally patients have suffered very much afterward, as if somehow the suppressed pain pro- duced an exaggerated reaction. Occasionally too deep suggestion has left a curiously susceptible condition, and patients have suffered more in the after-treatment than would otherwise have been the case. As a rule, a number of seances of hypnotism must be held, in order that the operator may be assured that he can produce a condition of hypnosis sufficiently profound for surgical purposes. This has many disadvantages. A sort of hypnotic habit has been developed in some people, manifesting itself during convalescence, so that almost any un- usual incident would recall the hypnotic state. As a consequence of all these disadvantages, hypnotism has never been generally used for sur- gical anesthesia. There is no doubt, however, that in a great many per- MENTAL INFLUENCE IN ANESTHESIA 649 sons hypnotism can be employed to secure almost complete anesthesia for shorter surgical operations. The pulling of teeth, the opening of a boil or even a carbuncle, the dilatation of a sinus, the removal of a wart or of a small mole, or even of a wen, may be accomplished in the hypnotic state. The hypnotism in these cases is not something special to the operator, but is due to the confidence that the patient has in him, so that, at his persuasion, the mind becomes concentrated on a single thought, with the senses dulled except the sense of hearing, and that re- ceives only the impressions that the operator desires to give. Hyp- notism is not a mysterious process, but a state that can be induced in susceptible persons by anyone who has the confidence of the subject and sufficient assurance in his own power to accomplish it to make the pa- tient accept his declaration. Charlatanism and Hypnotism. — Undoubtedly some of the minor operations that are done by wandering advertising physicians who re- move teeth or open boils or abscesses without pain are accomplished in a state resembling, if not identical with, hypnotism. In country places particularly people are likely to have an exaggerated sense of the wondrous powers of men who claim to have the faculty of producing in- sensibility to pain by rubbing something over the part that is to be af- fected by the operation. They become so much occupied with this thought, and with the positive assurance given them of the painlessness of the operation, that they feel very little or no pain. The wonderful '^pain killer" that has been applied is then sold to them, but it practi- cally always fails to produce similar results to those first experienced when its maker is not present and producing a very definite mental effect. SUGGESTION Suggestion Instead of Hypnotism. — In recent years hypnotism has fallen into disrepute once more, and its dangers have come to be em- phasized. These are mainly connected with frequently repeated hypnotic seances. Many who are interested in the influence of mind on body have come to realize, however, that most of the effects that can be se- cured through hypnotism can, with equal patience and persistence, and with the confidence of the physician and the trust of the patient, be ob- tained by suggestion in the waking state. It is probable that this would never be true for complete anesthesia such as would permit the per- formance of a serious surgical operation. There is no doubt, however, that the operator's mind can to a great degree influence the suscepti- bility to pain, and so predispose the patient's mind and preoccupy his attention that the solicitude before operation is greatly lessened and the preliminary stage of excitement during inhalation anesthesia is prac- 650 ANESTHESIA tically obliterated. This is not of trifling importance, for it greatly diminishes the amount of the anesthetic necessary to produce complete insensibility to pain. It must not be forgotten that the mortality after operations in our time is distinctly increased by the after-effects of the anesthetic, and that the less of the agent that is given the better the outlook. A careful application of suggestion, then, as an auxiliary, may not only save the patient worry and the lowering of resistive vitality, but may tend at least to be actually life-saving. Psychic Influences and Surgical Anesthesia. — The principles of mental influence in the production of absolute anesthesia and hyper- esthetic conditions have a valuable application in surgical anesthesia. If the patient's mind is properly prepared, if his confidence is secured, if solicitude is removed, if anticipation is blunted, then much less of an anesthetic is needed to bring the patient into insensibility to pain than would otherwise be the case. A terrified, excitable patient requires a large amount of an anesthetic that must be administered in heavy, con- tinuous doses, and, even with that, often does not exhibit complete re- laxation and absolute insensibility. It is extremely important, then, that patients be assured as much as possible with regard both to the operation and the anesthetic itself. They should not be allowed to be in or near operating rooms where there is any manifestation of pain on the part of the preceding patient, nor in contact with those who are coming out of the anesthetic, nor near those who are exhibiting any lack of control during the early administration of the anesthetic. Sur- geons should bear this in mind, and not discuss subjects which in this excitable stage may unduly impress and perhaps terrify the patients about to be anesthetized. As far as possible the anesthetist should not be a stranger to them, or, if a stranger, should be introduced under cir- cumstances that impress them with the idea that the going under anes- thesia will be easy and that there will be absolutely no reason for solici- tude during its course. Anyone who has seen a man gain the full confidence of patients and take pains to reassure them, telling them soothingly to concentrate their attention on deep breathing, and controlling quietly the first sign of ex- citement, and bring them fully under an anesthetic without any diffi- culty and with only a few drops of the anesthetic material, will realize how important the patient's state of mind is in anesthesia. It has been suggested that the patient should be asked to put the hands to- gether quietly across the chest, and that, whenever there is a tendency to separate them, the suggestion should be given to keep them together. The constantly repeated suggestion of keeping the hands together and breathing deeply, if given quietly, so occupies the patient's attention that the excitable stage of anesthesia often passes over unnoticed, or with MENTAL INFLUENCE IN ANESTHESIA 651 only the beginning of movements of the muscles controlled at once by gentle contrary suggestion. Classes of Patients Where Psychic Influences Ake Most Useful. — This method is particularly important for patients who are nervous, excitable, and inclined to be terrified over the operation. Un- less negroes have complete confidence in the operator and the anesthetist, there is almost sure to be a disturbing excited stage. On the other hand, there are men who have the confidence of such patients and are able to bring them under the anesthetic influence without any difficulty. The same thing is true of children. Some one whom the child knows and trusts implicitly, but who is not likely to grow excited or to show, even by the slightest sign in voice or action, that they are worried, is a great help in bringing the child under anesthesia. The stroking of the child's hands by this person, and repeated suggestions to breathe deeply, to keep the hands together and not to move the feet, will usually bring the little patient under the anesthetic without any difficuly. This rep- resents a real mental influence due to suggestion, and it is of great value. It can be adapted to various patients so as to produce the best possible effects. In its absence there may be trouble and excitement, and force may have to be employed; the patient, in such an event, is not so well disposed to resist the influence of the shock of the operation. With it everything goes smoothly, and a waste of precious vitality, often needed for the strain of the operation, is spared. Local Anesthesia and Mental Influence, — The varying phases of in- terest in local anesthesia illustrate very well how large a role mental in- fluence plays in these conditions. Some surgeons can perform almost any operation under local anesthesia without complaint on the part of the patient. Others, who employ much more of the nerve-obtunding drugs, are imable to accomplish anything like the same amount of surgical intervention, even this being accompanied by rather serious complaints on the part of the patient. Many a young physician who has seen an experienced surgeon perform a rather serious operation by means of in- filtration anesthesia has gone home impressed with the idea that he could surely do a much simpler operation in the same way. He has been inclined to think that the chemical agent used was the most im- portant portion of the anesthesia. He may have found, however, that his patient complained very bitterly. Often such an experience has been enough to make him give up the idea of using local anesthesia. What he needed to realize, however, was that the patient was not so deeply influenced by him as by the more experienced surgeon, and that, as a consequence, even the slight pain produced, owing to nervous irrita- bility, became exaggerated after a time, giving rise to the patient's bit- ter complaints. 652 ANESTHESIA Importance of Personality of the Anesthetist. — The surgeons who have reported success with local anesthesia have been men of a special personality capable of attracting the confidence of patients, and of making them feel absolutely sure of their physician's assurance that there was to be no pain. Schleich did much, some fifteen years ago, to develop local anesthesia by infiltration methods. Numbers of physi- cians who visited him thought they possessed his full secret when they had learned his technique and secured his formulae. Many^ of them found, however, that, while Schleich's patients seemed to suffer no pain even from serious operations, their patients often sufl^ered pain from even trifling surgical intervention. Everywhere that local anesthesia was being employed at that time the personality of the operator was the most interesting feature of the work. The mental element was an essen- tial factor in the insensibility to pain. In this country our local anes- thetists have been of the same class. Mental Influence as a Valuable Auxiliary. — No matter what the form of anesthesia, it is an extremely helpful auxiliary to have the mind favorably disposed toward it, and the patient properly assured and con- fident of the successful issue of both the anesthetic and the operation. Undoubtedly many of the adjuncts of various kinds that have been introduced, and that for a time were efficient in producing anesthesia without excitement in conjunction with ether and chloroform, have owed their success more to the influence on the patient's mind than to their own efficiency. They have come and gone, acquiring reputations and then losing them, as remedies of all kinds have done which affected the mind, because they were given with a strong suggestion that they would produce a definite effect, and this effect was manifested as a consequence of the suggestion. Certain it is that almost anything given the patient with the promise that it will make the taking of the anes- thetic easier and will do away with its worst effects will greatly lessen the stage of preliminary excitement. Patients who have heard much of the awful choking and suffocating sensation produced by an anes- thetic, and who dwell on the thought, do not succumb to its effects very readily, and more of the anesthetic is generally required to bring them under its influence. Physicians, as a rule, go under anesthesia badly for this reason. Suggestion works both favorably and unfavorably, ac- cording to its significance. Deep Breathing and Concentration of Mind. — Hack Tuke, in his "Influence of the Mind on the Body," ^ records some stories of anes- thesia produced by the thought on the part of the patient that he or she was inhaling an anesthetic. Such experiences are not uncommon. Every anesthetist is likely to have had patients who began to manifest symptoms of disturbance of consciousness at least, if by chance the in- 1 Philadelphia, 1889. MENTAL INFLUENCE IN ANESTHESIA 653 haler without any anesthetic was placed over their mouths and they were told to breathe deeply. Deep, rapid breathing will of itself produce cer- tain changes in the blood which bring about a certain amount of anal- gesia ; and, if patients are told to do it, and have emphasized for them its effect upon their pain sense, it is rather easy to open boils or abscesses with the production of very little pain. It is probable that in all cases it is of advantage to properly compose the patient's mind and begin the anesthesia by deep breathing through the inhaler before any anesthetic is put on it. A few deep breaths, with the concentration of mind on the breathing, and some soothing words, will usually put a patient in a bet- ter disposition to take the anesthetic without excitement than any pro- cedure even more complex than this. Preliminary Medication and Mental Influence. — Certain substances, opium, for instance, when used with discretion, seem to predispose the patient to take an anesthetic without excitement and with much better control. If given an hour before the administration of an anesthetic, even a small dose will, especially in conjunction with a proper reassur- ance of the patient, produce a state of mind in which the anesthetic will be taken without difficulty. In nervous, excitable persons some such treatment is advisable for the sake of its good effects. Sometimes bromids taken for several days will produce a more placid state of mind than would otherwise be the case. These drugs, however, will not re- place the personal element of strong mental influence. Experience has demonstrated that patients of the most varied ages, types, and tempera- ments go under an anesthetic without difficulty in the hands of a skilled anesthetist, while one without skill required help and produced rather serious stages of excitement in exactly the same classes of pa- tients. This personal influence is largely an individual matter, but, if the influence of the mind in the induction of anesthesia is properly rec- ognized, it is probable that much of its valuable help can be secured by anyone who deliberately tries to employ it as an auxiliary. PART II HYPNOSIS IN ANESTHESIA H. W. Frink, M.D. Hypnosis: The Different Degrees of Hypnosis and Some of the Phenomena Accompanying Them; Factors Which Influence Suggesti- bility; The Attitude of the Hypnotist; Methods of Inducing the State of Hypnosis; The Induction of Anesthesia. 654 ANESTHESIA The Different Degrees of Hypnosis and Some of the Phenomena Accompanying Them. — Every person is in some degree susceptible to suggestion, but hypnosis cannot be induced in everyone, nor can all hypnotizable persons be influenced to the same extent. Three degrees of influence or stages of hypnosis are described by For el, while other writers make as many as seven or eight. Forel's classification, which seems to be the simplest and most practical of any, is as follows : (1) Somnolence, or Drowsiness. — The subject influenced only to this degree experiences more or less lazy or sleepy feelings. He can open his eyes, however ; is perfectly conscious of all that goes on ; and, by making an efl^ort, he can resist any or all of the hypnotist's suggestions. (2) Hypotaxis, Charme, or Light Sleep. — Here the subject cannot open his eyes. He is aware of all that takes place, but certain suggestions given by the hypnotist cannot be resisted. Thus, when he receives the suggestion that his arm is stiff, it becomes so, and he is un- able to bend it. If he is told that one of his limbs is paralyzed he cannot move it, or, if told to clap his hands together or to perform any like movements, and then given the suggestion that he cannot stop these movements, he is unable to do so. In this stage some sensory phe- nomena, such as feelings of weight in the limbs, or of itching or tickling in the skin, etc., may be produced. A touch of a pencil, for instance, is felt to be hot, cold, or painful, according to the suggestion given. Some degree of hypesthesia and, occasionally, visual or auditory hallucina- tions may be successfully suggested. Though the subject is quiet and appears to be asleep, there is no amnesia, and upon "awaking" he re- members everything that has taken place. (3) Somnambulism, or Deep Sleep. — This degree of hypnosis is characterized by the presence of amnesia for everything that occurs during the period of trance. In deep somnambulism suggestibility is very great. Subjects, while en rappori, believe everything the hypnotist tells them, almost any conceivable effect upon the voluntary muscles can be produced, and even involuntary motor or secretory mechanisms may be influenced (e. g., sneezing, defecation, perspiration, menstruation, etc.). All sorts of hallucinations, illusions, and delusions are produced. Thus a good subject will accept suggestions that he is a great orator, a baby, or even an inanimate object, and he will act the part in a most striking manner. Hyperesthesia, paresthesia, or anesthesia of any of the senses may be induced. Though, in response to the hypnotist's command, the subject will carry out the most complicated actions, if left alone he appears to be sound asleep, and orders, shouts, slaps, or pinches from a third person have no apparent effect upon him either in stimulating him to any ac- tivity or in arousing him from his trance. Nevertheless the word "awake," whispered by the hypnotist, will at any time promptly ter- HYPNOSIS IN ANESTHESIA 655 minate the sleep. Suggestions during the trance may be so given as to have their effect either directly carried over into the waking state or pro- duced after an interval of waking, at a given time or in response to a given signal (post-hypnotic suggestion). Many persons after having once been deeply hypnotized are quite susceptible in the waking state, to the suggestions of the hypnotist, and various motor and sensory phe- nomena, even to surgical anesthesia, may be induced while the subject appears in all other respects to be entirely in his usual state of mind. The three stages of hypnosis here described show no sharp demarcation from one another, and this or any other classification is purely arbi- trary. There is little similarity to the stages of chloroform or ether anesthesia, for a subject may pass immediately into somnambulism without going through the first or second stages of infiuence, or, in other cases, in spite of the most prolonged and painstaking effort on the part of the hypnotist, amnesia and the other phenomena of the third stage cannot be produced. Generally speaking, surgical anesthesia is pos- sible only in the third stage. Though a certain diminution of pain sensibility may be produced in the second stage, complete anesthesia is rare, and cutting operations are seldom possible. To practically all somnambules one can successfully suggest that the prick of a pin will be painless, but it is quite a different matter to c'ause complete insensibility to the cut of knife and scissors. In very suggestible subjects absolute anesthesia can be obtained, and, either during the trance or post-hypnoti- cally, really extensive surgical operations may be performed without the slightest discomfort to the patient; but such instances are uncommon, and in not a few somnambules surgical anesthesia is an impossibility, while upon others only minor operations are possible. Whether or not somnambulism may be induced in a given subject depends in no small degree upon the skill of the hypnotist, but to a greater extent upon the suggestibility of the subject. Out of one hun- dred and nineteen cases, Vogt obtained somnambulism ninety-nine times, hypotaxis eighteen times, and somnolence twice. This percentage of somnambules is very high, and for the average hypnotist to equal this record by half would be no small task. Different operators influence to some extent from 80 to 98 per cent of their subjects, but not more than 10 per cent of those influenced could be rendered surgically anesthetic. Factors Which Influence Suggestibility. — Of the general factors which influence suggestibility age is the most important. Children under four or five years of age usually cannot be hypnotized, but from the 6th to the 16th year nearly all children are very readily influenced, and a large percentage of them can be made somnambulistic. After six- teen suggestibility diminishes very gradually up to about the forty-fifth year and then more rapidly. As a rule, old people are very hard to influence or are practically insusceptible. Sex and nationality have very 656 ANESTHESIA little influence upon suggestibility. Health is an important factor, and, speaking in general, well people are more easy to hypnotize than sick ones. This is especially true of mental health, and the neurasthenic, psychasthenic, and hysterical usually are resistant subjects. Idiots, low-grade imbeciles, and most of the insane cannot be hypnotized at all. Most writers believe that intelligent and educated people are more read- ily influenced than the ignorant and stupid. People accustomed to obedience, such as soldiers, servants, etc., seem to be more susceptible than those who are wont to command. It must be emphasized that there are no means of determining be- forehand whether a person may or may not be hypnotized readily, and the statements here made as to suggestibility in general are subject to a great number of individual contradictions. Subjects who present no evident difference in respect to age, education, temperament, intelli- gence, etc., show great and inexplicable differences in suggestibility. Thus one occasionally finds children who are quite unresponsive, while, on the other hand, a subject who, according to all expectations, should be difficult to hypnotize turns out to be extremely suggestible. A case in point is that of a woman of about fifty years of age whom I saw in con- sultation with J. H. Eichards. Because of her age and the fact that for twelve years she had suffered from phobias and various sorts of hysteri- cal manifestations, I thought that she would prove a very poor subject. As a matter of fact. Dr. Eichards induced deep sleep at the first at- tempt, and at a later date W. C. Cramp operated upon her for ingrow- ing toenail under hypnotic anesthesia. The Attitude of the Hypnotist. — It was quite the custom among many of the early hypnotists, as well as some of the later ones, to create, by the use of passes, magnets, and mirrors, or by the assumption of various peculiarities of voice and manner, an impression in the mind of the subject that the hypnotist either had at his command some mysteri- ous forces or was the possessor of peculiar and almost superhuman strength of will. Though, doubtless, such methods might occasionally impress credulous individuals in a way favorable to the induction of hypnosis, yet, in many more cases, an air of mystery is apt to antagonize the subject and to create a feeling of fear or distrust which makes hypnotization difficult or even impossible. On this account it is now generally considered an essential part of the technique of hypnotizing for the operator to explain to his subject that there is no magic con- nected with hypnotism, that it is a condition of mind into which nearly all normal people are capable of passing, and that its successful induc- tion in no way depends upon the operator's possessing a strong will or the subject a weak one; but merely upon the willingness and ability of the two persons to cooperate in carrying out a technique that can be learned by almost anyone. The subject is farther assured that hypnosis HYPNOSIS IN ANESTHESIA 657 will not, as is popularly supposed, "weaken his will" or render him re- sponsive to commands or requests which, in his natural state, would be strongly objectionable to him. In inducing hypnosis or the giving of suggestions, some hypnotists use a loud, commanding tone, and, so to speak, bully their subjects into the trance. Others, as does the writer, speak in a perfectly natural, quiet conversational tone and avoid any assumption of authority. Either method is effective, and ordinarily an operator succeeds best with the one more natural to him. Methods of Inducing the State of Hypnosis. — A very simple but not particularly efficient method is that mentioned by James. "Leave the subject seated by himself, telling him that if he close his eyes and relax his muscles, and, as far possible, think of vacancy, in a few minutes he will 'go off.' On returning in ten minutes, you may find him effectually hypnotized." The method of hypnotizing employed by Bramwell is the same, practically, as that used by Liebeaut, Bernheim, and many others. It has, perhaps, the most general use of any. Bramwell does not at- tempt to hypnotize his subject at the first sitting, but devotes this time to making the patient's acquaintance and ascertaining his atti- tude toward hypnotism. At the same time he endeavors to remove any erroneous ideas the patient may have, and he refuses to make any attempt to hypnotize until his patient is convinced of the desira- bility and safety of the procedure. At the next meeting Bramwell addresses his patient as follows : "Presently I shall ask you to look at my eyes for a few seconds, when probably your eyelids will become heavy and you will feel impelled to close them. Should this not happen, I shall ask you to shut them, and to keep them closed until I tell you to open them. I shall then make certain passes and suggestions, but I do not wish you to pay much attention to what I am saying or doing, and, above all, you are not to attempt to analyze your sensations. Your best plan will be to create some drowsy mental picture and to fix your attention on that. You must not expect to go to sleep. A certain num- ber of hypnotized persons pass into a condition more or less closely re- sembling sleep; few do so at the first sitting, however, and you must only expect to feel drowsy and heavy." After having given these instructions, he places the patient in a com- fortable chair, and darkens the room. Bramwell continues: "I re- quest the patient to look at my eyes, at the same time bringing my face slightly above and about ten inches from his. The patient's eyes sometimes close almost immediately. Should they not do so, I continue to look steadily at him and make suggestions. These are twofold: the patient's attention is directed to the sensations he is probably experienc- ing, and others which I wish him to feel are suggested. Thus: '^Your 658 ANESTHESIA eyes are heavy, the lids are beginning to quiver, the eyes are filling with water. You begin to feel drowsy; your limbs are becoming heavy; you are finding it more and more difficult to keep your eyes open, etc' Sometimes this produces the desired result; the eyes close and the first stage of hypnosis is induced. If this does not take place, I direct the patient to close his eyes, and make passes over the head and face, either with or without contact, repeating meanwhile appropriate verbal sug- gestions. This is continued for half an hour." The following method is the one generally employed by the writer. It is a combination of the methods of Yogt and Forel. Its chief advantage is that it gives ample opportunity for "training" the subject. The patient is seated in an easy-chair or reclines upon a couch. I then tell him to relax his muscles and to make himself as quiet and comfortable as possible. By lifting his hand and letting it drop, I test the muscular relaxation and do not proceed until it is quite complete. Then, holding my fingers a short distance above the patient's head and in such a position that he cannot see them without straining his eyes up- ward, I ask him to look at them for a few moments and then to close his eyes. I then press with one of my fingers well up in the middle line of the patient's forehead and direct him to keep his eyes closed, but to roll his eyeballs upward as if to look at the spot where I am pressing. I then say something to this effect: "You have noticed, probably, that your eyes have begun to feel a little tired and strained. While you keep your eyes rolled up, you will doubtless find that they tend to become more and more tired, that the lids begin to feel heavy, and, as you keep looking up, I think you will notice that it is harder for you to open your eyes than usual — the lids have a tendency to stick to- gether." Then, after lightly stroking the patient's lids and brow for a moment with my other hand, I say: "Now try to open your eyes slowly, and see if I am not right." In employing this technique, the hypnotist takes advantage of a physiological fact which is unknown to most patients. When the sub- ject strongly stimulates the third nerve in the effort of straining the eyeballs upward with the eyelids closed, it is practically impossible for him to open his eyes without looking down. On this account if, as the majority of people do, the subject follows directions exactly, and tries to open his eyes while his eyeballs are rolled up, he suddenly discovers that he cannot do so, and, unable to assign any other cause for this oc- currence, he attributes it to the hypnotist's suggestions. This apparently brilliant beginning impresses the subject and makes him think that all further suggestions will succeed eqiially well. Thus half the battle is won. It is not necessary to test him with his eyeballs lowered; one HYPNOSIS IN ANESTHESIA 659 merely says: "Yes, your eyelids stick fast together; you cannot open them; the harder you try to open your eyes the tighter they stick; this is the beginning of sleep,'' etc. In case the subject fails to follow directions and succeeds in open- ing his eyes, I betray no disappointment, but say expectantly, "What did you notice? Your eyes did not open easily" or something of the kind, and, in this way, try to lead the subject into admitting that he felt something. As soon as I have gained an admission, such as that the eyelids "stick a little," that he felt lazy about opening them, or some- thing of the kind, I have him close his eyes again and repeat the pro- cedure, adding: "This time your eyelids will stick harder. You may notice that you are becoming lazy and absent-minded, and consequently adverse to making any effort," etc. In this way I endeavor to increase by suggestion whatever the patient admits he felt and, at the same time, to introduce new suggestions. I continue to repeat the operation, and, when I see that the subject, at each repetition, meets with greater and greater difficulty in opening his eyes, I become more definite in suggesting, until, finally, I can say positively : "Your eyes now stick fast together; you cannot open them at all." While giving the above sug- gestions, I, at the same time, throw out occasional hints to the effect that a lazy, drowsy feeling is coming over the subject, and that he is be- ginning to go to sleep. This description of beginning the seance will, I trust, make clear the general scheme of this method of hypnotization, a consideration of which now follows. Introduce as Early as Possible Several Lines of Suggestion. — In doing this the hypnotist should avoid making definite statements that .such and such phenomena will appear, but should seek to bring about the beginning of the desired effects by hinting, verbally and otherwise, at their probable occurrence. The four lines of suggestion most con- veniently followed are : Inability to open the eyes, advent of drowsiness or sleep, involuntary rigidity of an arm, and heaviness of a hand. To create an expectation of drowsiness, I tell the subject, before at- tempting to hypnotize him, that it is a scientific fact that, if anyone pre- tends to be in a rage, he will actually feel a little angry ; if he kneels as if to pray, he tends to feel devout; and, in the same way, if the subject will assume a quiet and comfortable position, close his eyes, and relax his muscles as if be were asleep, he may expect to feel drowsy. The method of suggesting inability to open the eyes has been indi- cated. In suggesting rigidity of the arm, the limb is held as in Figure 275, with elbow and wrist hyperextended. I then bend his wrist very slightly back and forth until I feel a little resistance in either the flexors or extensors. Here I immediately bend the wrist in the direction neces- -660 ANESTHESIA sary to oppose this resistance. This gives the subject the impression that the muscles of his arm are becoming tense and introduces the line of sug- gestion desired. To suggest heaviness of the hand, I lift the patient's hand and then drop it. If his muscles are well relaxed, the hand falls heavily, and it is easy for him to be made to believe that it really feels heavier than usual. I assist the impression by taking hold of his wrist as if to lift it, and then letting it slip from my fingers as if it were very heavy. Push the Suggestion That Works Best Until Some Definite Effect Is Produced Which the Subject Cannot Resist. — When, either from what the subject says in response to my hints or from what I observe (for in- stance, I may see that the subject lifts his hand with diiJiculty or I may Fig. 275.— Suggesting Rigidity of the Arm. feel that the muscles of his arm contract), I conclude that one or an- other line of suggestion is beginning to produce some effect ; I direct my suggestions toward increasing this one effect. The more my suggestions work, the more positive I become in suggesting until I can say with con- viction that the efl'ect I am seeking is produced and that the subject cannot raise his hand, bend his arm, or open his eyes, as the case may be. I am always careful never to commit myself to a definite assertion unless I am sure that the subject already feels or will immediately feel what I tell him. In this way I avoid the danger of his thinking that this or that suggestion has failed with him. When One Phenomenon Has Been Successfully Suggested, Employ It in Producing New Ones. — Up to a certain point each suggestion suc- cessfully given increases the subject's suggestibility and makes him more ready to accept new suggestions. Also, a new suggestion is more HYPNOSIS IN ANESTHESIA 661 acceptable if it can be represented as the result of or dependent upon some already induced phenomenon. Consequently, if I succeed in pro- ducing irresistible heaviness of the subject's haiul, I suggest that his efforts to lift it have made him very tired and sleepy, that the feeling of weight is extending from his hand all over his l)ody, that even his Fig. 276. — Beginning of Sleep by Frink's Method. head is affected so that it becomes heavy and drowsy, and he finds him- self going off to sleep. Or, if I have made his arm stiff, one way of put- ting him to sleep is by telling him that his arm is being drawn to his head as if by a magnet, that the closer his arm comes to his head the more sleepy he becomes, and that by the time his arm touches his head he will be sound asleep. Endeavor to Get the Subject into the Third Stage of Hypnosis as Soon as Possible, hut Terminate the Seance Rather Than Give Non- effective Suggestions. — When I find that a subject immediately accepts my suggestions and that everything I tell him promptly produces the desired effect, I keep on until I have him soundly asleep and have in- duced automatic movements, anesthesia, and other phenomena of the third stage. But in cases where the seance proceeds less smoothly it is 662 ANESTHESIA necessary to be very cautious in suggesting, for, if one attempts too much at one sitting and gives suggestions that do not take effect imme- diately, the subject gets the impression that these suggestions will con- tinue to.be unsuccessful. Such an impression is difficult to remove, and operates as a -barrier against further progress in that particular direc- tion. On this account I content myself with what result's I can obtain from perfectly safe suggesting and terminate the sitting as soon as I 1 1 i Fig. 277. — Beginning of Sleep by Feink's Method. find myself on dangerous ground. To do this one need only say to the subject: "You are waking up now/' or, "When I have finished count- ing ten, you will be perfectly wide awake." After Each Sitting Ascertain Exactly- What the Subject Experi- enced and Plan the Suggestions to Be Given at the- Next Sitting on the Basis of This Information. — When the subject awakes, I ask him to describe in detail everything he experienced, and lead him on with ap- propriate questions if necessary. In this way I learn the extent and na- ture of the effect that each of my suggestions had upon him, and at the next seance I follow up those that promise well, and avoid the ones that HYPNOSIS IN ANESTHESIA 663 are ineffective. At the same time, if the subject's nervousness, curiosity or some misconception has interfered with his going to sleep, this will be disclosed and can be dealt with. In addition, any undesirable auto-sug- gestions that may have formed are brought to light, and may be over- come before they can do any harm. It will be found that some patients will feel a certain sort of pride if they have been resistant to suggestion. One may then call their attention to that fact, show them that the ability to resist need cause them no conceit, and thus prevent further trouble from such a source. With some patients it may be noticed that, though by suggestion an arm may be made perfectly rigid, yet as soon as the hyp- notist says "You cannot bend your arm," the reverse of the desired re- sult is obtained and the limb is promptly bent. These are persons who resent what they consider an attempt to deprive them of the "freedom of the will," and in dealing with them it is better to give such sugges- tions as "You will feel unwilling to bend your arm; the effort is a disa- greeable one," etc., until when it is perfectly clear that the subject has attempted to bend his arm, but without success, one can then say, "You cannot do it," At Subsequent Seances Continue the Subjects Training Until the Different Phenomena of the Third Stage May Be Induced Beadily or the Impossibility of Their Induction is Demonstrated. — Subjects who are in- fluenced only slightly in the first or second seance may often be made quite susceptible by careful training. An effect once produced on a given subject can always be reproduced without difficulty, so that at one seance it requires only a few moments to bring about the same degree of hypno- tization that existed in the preceding one. At each sitting, therefore, the hypnotist can begin where he left off at the preceding one, and continue by pushing those lines of suggestion which appear promising. Whatever that subject admits of having felt at the preceding sitting, the hypnotist endeavors to increase by further suggestions, and whenever any definite phenomenon is successfully induced it is employed in furthering some partly successful line of suggestion or in introducing a new one. In this way, by carefully analyzing the results of previous sittings and proceed- ing cautiously, one may change slight hypotaxis to complete hypotaxis, and then, by gradually suggesting amnesia, convert this stage, in turn, into somnambulism. For instance, when a subject tells me that during a sitting he felt drowsy, lazy, and absent-minded, I suggest at the early part of the next seance that he feels so lazy and absent-minded as to pay little attention to what I am saying. Later in the seance I tell him that he has been so inattentive, because of lazy and drowsy feelings, that when he awakes, he will experience some difficulty in recalling all that I have said to him. If, at the close of the seance, I find that my sugges- tions have had the desired effect, then, at the next meeting, I suggest still greater drowsiness and inattention, and greater consequent diifi- 664 ANESTHESIA culty in remembering in the waking state what has occurred. At subse- quent sittings I continue in the same way until complete amnesia is pro- duced. If, in five or six sittings, deep hypotaxis has not been produced, it is generally certain that surgical anesthesia is impossible, and therefore further attempts are practically useless. In any case where operation is contemplated, the hypnotist should arrange to see the patient at least half a dozen times before the date of operation. The Induction of Anesthesia. — In hypnotizing with a view toward surgical anesthesia, it is best not to run the risk of failure by beginning 1 Mm 1 1 ■ H f '> --T ***^"*'^^ ^^^I^H p w J ^s t V 1 »» ' ^H Fig. 278. — Induction of Anesthesia. to suggest anesthesia too soon. One should first get the subject into a state of somnambulism, or, if this cannot be done, into as deep hypotaxis as possible. Then one may begin by closing the subject's hand and pro- ducing rigidity of the whole arm. The subject is then told that the contraction of the hand and arm muscles begins to impede the circula- tion in his hand, in consequence of which he will probably become aware of a feeling of numbness in that region. He is then informed that in order to test this numbness the hypnotist will prick the back of the hand with a pin and that the pin will feel less sharp than usual. Instead of using a pin, however, the hypnotist touches the subject's hand with a sharpened match or a toothpick. If this works well, and the subject seems to believe that a pin has been used, greater diminution of sensi- bility is then suggested, and a real pin is then employed, though very lightly. The hypnotist continues in the same manner, suggesting in- THERAPEUTIC USES OE INHALATION ANESTin:TI(;S 665 creasing hypalgesia, and applying the pin with more and more force until even a vigorous thrust causes the subject no pain. After this it is well to suggest that not only is the pin thrust entirely painless, but that it is not felt at all — that is, that the part is both analgesic and anesthetic — "perfectly numb and dead, like a piece of rubber." When anesthesia or analgesia has been successfully suggested in one part of the body, it is always easy to reproduce it in any other part, and for so doing the preliminary suggestion of rigidity or other phe- nomena is unnecessary. In any case where an operation is contemplated the hypnotist should assure himself that he has the subject well under control, that anes- thesia can be produced both promptly and certainly, and that it is suffi- ciently deep. The depth of anesthesia should be put to rather severe tests, such as thrusting pins into the finger tips (with due care to avoid infection) or by touching the cornea after having suggested insensibility of that part. Before the operation, appropriate suggestions should be given with a view toward relieving the patient's mind of any anxiety or dread in regard to it and its consequences. The whole matter should be treated rather lightly, as if there could be nothing to fear and every- thing was sure to go smoothly. At the time of operation the patient may be placed upon the table and hypnotized there, but it is preferable to induce the hypnosis in an adjoining room and either let the patient walk or be carried to the table while in the hypnotic state. In any case, for the patient to see a great display of knives, scissors, and other instruments is decidedly un- desirable. During the operation the hypnotist should remain with the patient, and from time to time suggest that he continue to sleep quietly, that the field of operation is entirely without sensation, and that every- thing is going on nicely. The operating surgeons had best avoid refer- ences to cuts, blood, and other matters which might tend to have a dis- quieting effect upon the patient, who, though apparently in profound slumber, is not entirely unsusceptible to external influences. When the operation is finished, before awaking the patient, it is well to sug- gest that even in the waking state his wounds will cause him no pain and that the necessary dressings will give rise to no discomfort.^ 1 For other considerations of hypnotic therapeutics, see Tuke : ' ' Treatment by Hypnotism and Suggestion," 5th ed., London, 1907; Ford: "Hypnotism and Psychotherapy ' ' ; Hilzer : ' ' Hypnosis and Suggestion ' ' ; Bernheim : ' ' Suggestive Therapeutics ' ' ; Moll : ' ' Hypnotism ' ' ; Quackenbos : ' ' Hypnotic Therapeutics in Theory and Practice." CHAPTEE XVIII THEEAPEUTIC USES OF INHALATION ANESTHETICS Anesthetic Treatment for Special Conditions: In Eenal and Biliary Colic; In Acute Pain or Shock; In the Passage of Eenal or Biliary Calculi ; In Extreme Irritability of the Central Nervous System ; Convulsions of Infancy and Childhood; Puerperal Eclampsia; In Anemic Convulsions; Convulsions and Seizures Depending Upon Poi- soning, and Cerebral Diseases ; Use in Diagnosis ; Insomnia or Extreme Eestlessness ; Acute Mania; Nitrous Oxid and Oxygen; Some Miscel- laneous Applications of Ethyl Chlorid. Other Uses of Agents Employed in the Administration of An- esthetics : Ether in the Treatment of Infections ; Ether Irrigation of the Abdomen. ANESTHETIC TREATMENT FOR SPECIAL CONDITIONS Anesthesia has been used sporadically and, in some few instances and localities, regularly for special conditions or for diseases not yielding to surgical operations. In Renal and Biliary Colic. — In renal and biliary colic and for similar acutely painful seizures it has been used with great success. Now that the analgesic stage of all anesthetics, especially of nitrous oxid and oxygen, is more clearly recognized, it is probable that anes- thesia will be used more frequently than ever before for conditions just stated and for similar conditions. A patient in an acute seizure of renal colic, who might seriously object to being anesthetized to the sur- gical stage, would embrace the opportunity of the analgesic stage of any anesthetic. In Acute Pain or Shock. — In cases of acute pain or shock it is used for temporary relief, not with the idea of curing, but simply to afford time for recovery to take place without pain. When anesthetics are given for the analgesic qualities alone they should be employed only under the direct supervision of a physician. If cyanosis or unconscious- ]iess appear, the agent should be withdrawn, to be reapplied again solely for the relief of pain. 666 THERAPEUTIC USES OF INHALATION ANESTHETICS 667 In the Passage of Renal or Biliary Calculi. — In the passage of renal or biliary calculi, chloroform or ether by the drop method on gauze or a handkerchief affords speedy relief; also in the crises of locomotor ataxia. In Extreme Irritability of the Central Nervous System. — Wher- ever extreme irritability of the central nervous system exists, as in tetanus, strychnin poisoning, or convulsive affections, chloroform to the second stage will easily relieve suffering without affecting the conscious- ness. Hewitt records one case of a child kept more or less under the in- fluence of chloroform for thirteen days, one hundred ounces being used. It is necessary to administer the anesthetic only to the point where mus- cular spasm subsides, when it is discontinued. The anesthetic is to be reapplied only when tetanic spasm is imminent. If the rigidity is con- tinuous the administration must be maintained until signs of the rigid- ity disappear. It is unnecessary to state that, except in the presence of urgent indi- cations, these agents should not take the place of morphin or opium. When, despite the use of morphin or opium, acute pain persists, chlo- roform or ether may be administered for short periods to supplement the action of these drugs. Convulsions of Infancy and Childhood. — Convulsions of infancy and childhood are easily and safely treated with pulmonary anesthetics, administered to the analgesic stage. Ethyl chlorid is preferred, because its analgesic stage is longer than that of any other inhalation anes- thetic, and because it is the preferable anesthetic for children, in the opinion of many anesthetists. Puerperal Eclampsia. — Chloroform has been used for a number of years for puerperal eclampsia. Care must be taken, however, if the pa- tient is cyanosed. In these cases ether is the safest drug. In Anemic Convulsions, Convulsions and Seizures Depending Upon Poisoning, and Cerebral Diseases. — In anemic convulsions, convulsions and seizures depending upon poisoning, and cerebral diseases it is better to use nitrous oxid and oxygen, with a nasal inhaler, for the analgesic effect than to use chloroform or ether, especially chloroform, inasmuch as these latter drugs in themselves sometimes, under certain conditions, induce serious after-effects. Use in Diagnosis. — General anesthesia is frequently employed to produce muscular relaxation where diagnosis of certain conditions is doubtful. The selection of the anesthetic in these instances would de- pend upon the conditions already stated. Unless contraindicated, nitrous oxid and oxygen is the best agent for such conditions as 'Tiys- terical contractions," phantom tumors, and malingering. Insomnia or Extreme Restlessness. — In insomnia or extreme rest- lessness morphin and similar drugs are often ineffectual. The patient 668 ANESTHESIA may be in such a condition that the usual measures necessary to pro- duce a quiet state, such as warm baths, massage, etc., caimot be used except to very great disadvantage. Under these circumstances it is per- fectly justifiable to produce anesthesia and to inaugurate the necessary remedial procedures. Mortimer ^ treated a vigorous man who had had no sleep for many days and nights in spite of various hypnotics. The anesthetic was administered, and the patient remained asleep for four hours. By giving a little more anesthetic at longer intervals the patient remained asleep for two hours longer. The rest of the night he re- mained quiet instead of wandering about. The next morning he was rational, had a bath, and ate a good breakfast. He slept most of the day and the following night, awakening quite recovered on the second morning. Acute Mania. — In cases of acute mania, either temporary or recur- rent, if the condition is apparently dependent upon no perceptible or A. M. P. M. TEMP. 3. P. *^ A-^I.^Lf ^- ft. ^- '"' ^.-^ ■^l.® S- >%fK- „•? „« ^ •¥ .W =UL^.-~ • s ■• ;i02.2°F.) 39 (100.4 F.) 38 37 (96.e°F.) 36 (90?F.) 170 160 160 140 130 120 no 100 90 130 120 110 100 90 80 70 60 BO 4B 40 36 30 25 20 IB 10 6 A y r / \' \ A f- > „ - K> U- ~^ - \, % V > I «* ( f- [ If* * ■^ 1* •" " ' _j RESP.— o^— B. P. ++S++TEV.F.— — •- — PL.LEE — — 0-— Fig. 279. — Anesthesia in a Case of Acute Mania. organic lesion, it would seem, theoretically at least, that general anes- thesia Avould, — in connection with other remedies before, during, and after, — tend to lessen or shorten the usual period in which the patient may have to be confined. Anesthetics may be given with less danger for therapeutical pur- poses than when surgical interference is necessary. The first case, as far as we are aware, in which an anesthetic was given for the definite purpose of attempting to affect favorably the brain cells without injuring the body occurred at the instigation of one of us (J. T. G.) in March, 1913, Dr. Swepson J. Brooks and Dr. T. Drysdale Buchanan associated. The case was one of mania of ten or twelve years' standing. It is given in full to show that a patient may be 'Mortimer, J. D.: Brit. Med. J., Jan. 7, 1899. THERAPEUTIC USES OF INHALATION ANESTHETICS 669 successfully and easily anesthetized for a number of hours without com- plications or shock resulting therefrom. The case is suggestive of great possibilities in psychiatry, and is given here primarily for that reason. The patient was in full surgical anesthesia at 10 o'clock, and the anesthetic was discontinued at 4 :30 p. m., the patient being practically under the anesthetic for six and one-half hours. The result was entirely negative, as far as affecting the patient's condition favorably. It was satisfactory from an anesthetic standpoint. The patient came out of the anesthesia, and was entirely rational, with absolutely no unpleasant symptoms of any kind. The temperature, pulse, respiration, and blood pressure were taken at regular intervals, and the chart (Fig. 279) shows the result. The narcosis was started with one-quarter of a grain of morphin with l/150th grain of atropin at 9 o'clock. The pulmonary anesthesia was commenced with chloroform at 9 :55 by the drop method. Hour Temp. Pulse Reap. B.P. 1 Sleep! Stim. Medicine Nourish- ment Remarks A.M. 8.— 9 30 (Enema) : Saline Glucose I i O.i (per Hypo) : Morph. Sulph. gr. { Atrop. gr. jIjs 9.55 99.2 108 76 150 amination. 10 05 ed (drop). 10.15 10.20 90 120 96 96 96 96 (drop). 10.25 10.30 24 24 24 24 ministered (vapor). 10.3i 11. — • 11. OS 110 11.20 Slight snore — lid reflex — pupil slightly dil. ■ — eyeballs rolling. 11.30 '99.'8 96 96 24 24 110 98 11.45 Slight per.spiration — breathing easy. Pt. warm but not per- spiring. 12.15 96 102 102 102 96 96 96 102 96 112 96 108 24 24 24 24 24 24 24 30 30 24 100 100 lOOi 100 100 115 312 114 114 112 12.30 Slight perspiration — eyeballs rolling. 12.45 P.M. 1. — do. 1.15 do 1.30 do. 1.45 2.10 2.20 2.40 3.10 (Enema) : Olive Oil 3.40 30 116 Massage — Alcohol rub. 3.45 4.00 99.8 ioo" 108 108 102 120 1 30 30 24 30 114 120 118 120 4.15 Slight perspiration. 4.30 4.45 Amt. Ether used 5ix 670 ANESTHESIA and was gradually changed to ether by the drop method. At 10 o'clock the patient was in full surgical anesthesia, and at 10 :35 oxygen and ether by the vapor method were substituted. This was continued to the end. In acute mania or other mental condition the alimentary canal should be thoroughly evacuated, and when the patient is under the anesthetic lecithin, olive oil, and saline should be continuously admin- istered with the idea of having enough lecithin absorbed to affect the brain cells favorably. The patient should be given enough morphin toward the close of the pulmonary anesthetic to continue sleep, so that he will awake in as nearly a natural manner as possible. The table on the preceding page and chart (Fig. 279) show the result of this anesthesia. Nitrous Oxid and Oxygen. — Under the influence of nitrous oxid with 20 per cent oxygen, Klikowitsch ^ found in the majority of healthy individuals accelerated cardiac contractions, diminished pulse waves, rarer and deeper inspirations. In cases of weakened heart action an unfavorable influence upon the heart not only failed to occur, but a favorable effect was actually demonstrable. The cardiac contractions, while somewhat diminished in number, were increased in efficiency. For these reasons, as well as on account of the beneficial influence on attacks of angina pectoris, on vomiting and cough of reflex origin, Kli- kowitsch employed nitrous oxid for therapeutic purposes. Some Miscellaneous Applications of Ethyl Chlorid.^ — To Differ- entiate Betv^een a Neuralgia op Central and One of Periph- eral Origin. — The theory is that if the lesion be central no inter- ference along the course of a centripetal nerve will alter its manifesta- tion ; while if the trouble is with terminal nerves, when communicatien between the periphery and the centers is cut off, all pain will disappear. The method is to freeze the tissues between the apparent lesion and the spinal canal or cranium either by freezing, as done for local anes- thesia, or by "reinforced freezing,^' i. e., by injecting a quantity of dis- tilled water beneath the skin over the part to be frozen or directly into the tissue until an appreciable bulging is produced, and then directing the spray of ethyl chlorid on this spot. The water will become ice, and the deeper tissues will be frozen or thoroughly chilled. "Coin" freezing is accomplished by placing a coin of suitable size and wet with water on the skin and spraying ethyl chlorid on it, when "a congelation" less severe than reinforced freezing, more severe than ordinary cutaneous congelation and one more accurately localized is obtained. To Differentiate Neuritis from Neuralgia. — "Neuralgia of an accessible nerve treated by freezing near its point of exit and failing to yield to repeated applications of the spray is not a veritable neuralgia, but a neuritis or a complicated neuralgia." ^Quoted by Brunn: "Die Allgemeine Narkose, " 1913, 325. ^Abrams: Am. Med. Surg. Bull, Dec. 15, 1895, 1487-1490. THERAPEUTIC USES OF INHALATION ANESTHETICS 671 As A Means of Localizing Pain. — If the area of pain is large, or there are many painful points, the pain will not cease until the exact spot of origin is frozen. In this way Abrams has discovered out of many cicatrices the one causing pain, a small neuroma, and a carious tooth not otherwise suspected. To Differentiate Many Neuralgic Affections of the Head and Thoracic and Abdominal Parietes from Visceral Diseases. — For this freezing is usually necessary along the intercostal nerves at their exit from the vertebrae. In this way symptoms that have been or could be interpreted as disease of some viscus have been referred to their true origin. OTHER TJSES OF AGENTS EMPLOYED IN THE ADMINISTRATION OF ANESTHETICS Reference (Chapter II, p. 91) has been made to the use of vari- ous agents which have been found, from laboratory experimentation and clinical experience, to modify the action of inhalation anesthetics. Reference will be found in Chapter XV, p. 598, to the use of ether as an antidote to the various agents employed for purposes of spinal analgesia. Ether in the Treatment of Infections. — We come now to the con- sideration of ether in the treatment of various infections. While this may be said to be apart from the subject of anesthesia, it has a practi- cal bearing with which the anesthetist should be familiar. Souligoux ^ has habitually and successfully employed ether in the treatment of peritoneal infections. He was led to this in 1891 by the following observation : In his service as an interne, with Leport, he was in charge of a man, both of whose legs had been crushed by a heavily loaded truck. The legs were reduced to a mass with crushed bones, which protruded from the midst of the large wounds, and there seemed nothing left but a double amputation at the thigh, to which the patient refused to submit. Souligoux carefully cleansed the wounds and poured in a liberal supply of ether, after which the two legs were put up in plaster. To his extreme astonishment, no infection occurred, and the patient's legs were preserved. He believed this to be due to the ether, which is very volatile and which had penetrated into all the corners and irregu- larities of the wounds, thus permitting their disinfection. Since that time he has washed all wounds with ether, and employs ether also for all superficial infections, lymphangitis, erysipelas, etc. Mode of Application. — The mode of application is as follows : In 1 Souligoux : ' ' Sur 1 'emploi de 1 'ether dans les infections, ' ' Bull, et Mem. Soc. de Chir. de Paris, Feb. 25, 1913, No. 7, 293. 672 ANESTHESIA a case of lymphangitis of the arm, for example, the limb is carefully washed with water and soap, as if to prepare for operation. After the skin has been wiped dry the entire affected region is wrapped in bandages, on which a liberal supply of ether is poured. The part is then wrapped in oiled silk, which is held in place with straps, which are tightened at the two extremities of the dressing, so that the ether can only evaporate slowly, and, to guard still further against evaporation, the limb is surrounded with a thick layer of non-absorbent cotton. Eesults Obtained. — The results obtained with this treatment are excellent, according to Souligoux, who has been able to obtain many cures in cases of grave infections. Ether has been employed by him in this manner in several hundreds of cases, always with commendable re- sults. Ether Irrigation of the Abdomen. — Since 1C91 he has introduced ether into the peritoneal cavity of guinea-pigs without harm. He did not venture to experiment in this way upon man, however, until 1912. This was done under the following conditions: In July he was called to see a patient who for eight days had suffered from intestinal obstruc- tion, with entire arrest of feces and gas, and stercoral vomiting. On the sixth day a laparotomy was performed for making an artificial anus. The iliac incisions were followed by the escape of gas and fecal matter from the abdomen, showing the existence of a perforation of the intes- tine, which required closure. Median laparotomy was performed. The abdomen was filled with fecal matter and gas; the bloated coils were covered with false membranes, and, after a prolonged search, a perfora- tion was found on the cecum, the size of a quarter. This was closed. Eegarding the patient as doomed, remembering his experience with ether in 1891, and being aware of Morestin's frequent employment of ether in abdominal operations, Souligoux poured ether into the abdomen,- upon the coils, into the small pelvis, — in other words, applying a thor- ough irrigation of the abdomen with ether. After careful wiping two drains were placed, one toward the small pelvis, the other toward the upper portion of the abdomen. To the great surprise of Souligoux, the patient made a good recov- ery, and he has since made free use of ether, with excellent results, in all abdominal interventions associated with pus. Marcille, according to Souligoux, followed the same procedure in sur- gical cases, as a routine method. The following is a summary of his ob- servations. Clinic Cases. — (1) Six patients, operated upon, with peritoneal infection, through ruptured tubal pregnancies. In each instance the peritoneum of the small pelvis and the affected coils of intestine vv^ere wiped off with ether-soaked bandages. He obtained six cures. (2) Seventeen patients, operated upon, with strangulated hernia. THERAPEUTIC USES OF INHALATION ANESTHETICS 673 In each instance the coil was washed with ether. All the patients heard from were cured. (3) Three patients, operated upon, with abdominal wounds and contusions, (a) Contusion, at 9 a. m. Operation, at 10 p. M. A per- forated coil, turbid fluid in peritoneal cavity, found. Copious ether irri- gation. Drainage. Cure. (b) Knife wound of abdomen, operated upon in third hour. A divided coil, a small perforation of another coil, two wounds of mesentery, found. Copious ether irrigation. Drainage. Cure, (c) Case of frightful abdominal traumatism, the individual be- ing practically cut in two, the wound extending from Scarpa's triangle on the right side to the left iliac fossa. Kepair of the numerous vascu- lar and visceral wounds. Irrigation with ether. Death during the night. (4) Three cases of general peritonitis, operated upon. Ether; free drainage. Two cures; one death. (5) Infarct of entire large intestine and two meters of small gut, all contained in an enormous eventration. Operation. Part of these coils ;were gangrenous; stercoral abscesses had formed. Eesection of the en- iire mass contained in the eventration, involving the entire large intes- tine as far as the iliac flexure, and two meters of the small intestine. Free ether irrigation. Eeestablishment of intestinal functions; gas and stools. Good pulse next morning. Death from syncope after thirty-six hours. (6) Eupture of stomach, through ulcer. General peritonitis, with large amount of purulent fluid, false membranes in intestine found upon operation. Suture of the perforation. Free ether irrigation. Drainage. Cure. (7) Compound fracture of forearm bones. Badly soiled wound. Washed with ether, and sutured without drainage. Healed by primary union. Observations. — It appears, from the sum-total of these observa- tions: (1) That irrigation of the peritoneal cavity with ether is in uo way injurious. In all the cases where Souligoux employed it he noted that the coils of intestine became pink, and contracted under the action of the ether; (2) that this irrigation seemed to have a powerful action as a disinfectant of the peritoneum. In the discussion of Souligoux's paper Cuneo stated that ether dress- ings, according to the technique of Souligoux, had been employed by him in cases of lesion of the extremities, usually lesions of an inflamma- tory character, such as panaris, phlegmons, etc. Excellent results were obtained by this method. On the other hand, the idea of pouring ether into the peritoneum did not appeal to him. The observations of Souli- goux did not seem to him to be demonstrative, and the cures appeared to be especially referable to the timeliness of the intervention. The sup- 674 ANESTHESIA pression of the cause of complications was a factor in the success. The question of drainage he regarded as secondary in itself. He had be- come convinced of this by obtaining a considerable proportion of cures in general peritonitis of appendicular origin, through the simple abla- tion of the appendix, and closure, without drainage. There is nothing, in his opinion, to permit the claim that in the observations of Souligoux the cure was due to the irrigation of the peritoneum with ether. Souligoux, in replying to the remarks of Cuneo, said the latter had not well understood the observations described. He reiterated some of the details of the case of obstruction of eight days' standing. The per- foration, he said, may be assumed to have coincided with the severe pain which was felt at this time. There was an inundation of fecal matter and gas in the abdomen. He had had so little confidence himself in the recovery of the patient that when he saw her in the evening he be- lieved he had made a mistake in the room, and left without speaking to her. On learning of his mistake he returned, finding the woman in fairly good condition. He was unable to believe that her recovery was en- tirely independent of the ether. He was convinced, from his observa- tions, that ether is not only harmless, but may be very useful in the treatment of peritoneal infections. CHAPTER XIX THE MEDICO-LEGAL STATUS OF THE ANESTHETIST John W. H. Crim Introduction : Police Power ; The Medical Profession Established ; Contest Between the Schools of Medicine; The Status of the Physician. The Physician's Liability: Ethical Liability of the Physician; The Civil Liability of the Physician ; Malpractice ; Liability of the Spe- cialist; The Criminal Liability of the Physician; Gross Ignorance or Negligence ; Statutory Liability. INTRODUCTION An examination of the vast number of decisions of the higher courts of the several States of the United States discloses the fact that the discovery and use of anesthetics ^ by the medical profession have had little or no effect upon the well-established principles of medical juris- prudence, and the profession of the anesthetist, of inestimable im- portance to the medical profession, and consequently to society in gen- eral, has found no place either in our courts or legislatures. At the outset it may be said that only those having qualifications of a physi- cian ^ or dentist should be permitted to administer anesthetics ; that it should be made a penal offense in every State for any person other than a legally qualified medical or dental practitioner to administer either a general or local anesthetic or a drug for the purpose of produc- * That which produces insensibility to pain: State v. Baldwin, 36 Kan., 1. ^ The term "physician" is here used in a broad sense, inchiding all who are lawfully engaged in the practice of medicine : Harrison v. State, 102 Ala., 170. At one time the term "physician" was employed in contradistinction to that of ' ' surgeon, ' ' but the modern use of the term includes those who perform surgery as well: Alison v. Eaydon, 4 Bing., 619; Wetlierel v. Marion County, 28 Iowa, 22; Little v. SMer, 33 N. J. L., 507; Matter of Hxmter, €0 N. C, 447. The term "Physician and Surgeon" is not limited to any one school of prac- titioners: Eaynor v. State, 62 Wis., 289. Osteopaths hardly come within this classification, unless they have pursued suc- cessfully an accepted course of study in medicine. For statutory definitions of above terms, see Public Health Law New York, 1909. 675 676 ANESTHESIA ing a state of unconsciousness during any medical, surgical, or dental operation. Dentists should be permitted to administer such anesthetics, general and local, as are necessary in the practice of dental or oral surgery and medicine, and should not be permitted to give either a local or general anesthetic in other medical or surgical operations or during childbirth. To determine the fundamental responsibility of an anes- thetist, one must look to the general principles of law which apply to the physician in the ordinary practice of his profession, with this ex- ception: the practitioner holding himself out to the public as an anes- thetist is properly considered a specialist, and is therefore held to a commensurately higher degree of skill and learning, in so far as the administration of anesthetics is concerned, than the ordinary practi- tioner.^ It will therefore suffice, for the purposes of this chapter, to indicate the general principles which define the duties of the physician with regard to his ethical, civil, and criminal responsibility, and to dis- ^ In this place it is appropriate to insert a summary of views relative to the training and status of the anesthetist. Hellman (N. ¥. Med. J., 95, No. 22, 1146) considers that no one without a medical training can ever become an expert anesthetist, and that nurses, sisters of mercy, and others should be excluded from general anesthetic work. The ad- ministration of anesthetics is legally medical practice, and as such may be han- dled only by graduate physicians in New York. However, we may point out that instruction in the practical administration of anesthetics should be a requisite part of the regular medical and dental courses. On the training required by the anesthetist, see the discussion in J. Am. Med. Assn., 5S, No. 20, 1614-5; and on the teaching of anesthetics, see an earlier paper, ibid., 51, No. 14, 1167. Chipman {Va. Med. Senii-Mon., 15, No. 12, 278) discusses the general signifi- cance of the term ' ' anesthetist. ' ' In the * ' paid anesthetist system, ' ' the anes- thetist gives all anesthetics, in private- cases receiving remuneration from the pa- tient, directly or indirectly, while with ward cases he either administers himself or has an interne give the anesthetic under his direction, and for these cases he receives no compensation. This system, Chipman maintains, is a long-delayed need. He considers that the trained anesthetist should play a very large part in reducing the death rate to a minimum. "The Trained Anesthetist" has been discussed by Porter. {Lancet-Clinic, 103, No. 25, 641.) He thinks that the administration of anesthetics should only be done by the trained man and that he should be an expert. He goes on to say: "Surgeons should insist upon having a trained anesthetist for all operations. . . . The anesthetist 's work is the equal of any other special line of work. ' ' Abernethy {Southern Med. J., 3, No. 8, 489) has treated of the anesthetist as a specialist. In the administration of a general anesthetic the exercise of judgment and skill is necessary, and this can only be obtained through special study and experience. As much care should be exercised in the administration as in the performance of an operation; and the anesthetist should have, and does have in properly regulated cases, as much responsibility as the surgeon. On the general practitioner as an anesthetist, see Moriarta: J. Am. Med. Assn., 53, No. 10, 768; and, on the professional anesthetist, consult Metzenbaum: Ohio State Med. J., 6, No. 3, 124. THE MEDICO-LEGAL STATUS OF THE ANESTHETIST 677 cuss, in appropriate places, the legislation and decisions pertaining to the administration of anesthetics by physicians, surgeons, anesthetists, and dentists. Police Power. — The application of the principles of law to the relations between physician and patient has its source in the right of society to prescribe rules of human conduct which conduce to the gen- eral welfare, that is, the police power inherent in sovereignty; accord- ingly, it is to the police power of a State ^ that society looks for protec- tion from ignorance, superstititon, and quackery in the medical profes- sion. The limitation upon legislatures in enacting statutes for the pur- pose of regulating the practice of medicine is measured by the extent of the police power; and, conceding that the protection of public health is of vital importance in modern government, a most casual examination of the early legislation, or the want thereof, reveals the inadequacy, as it were, of the ancient forms of government in this respect. For example, we are told that, under the Eoman civil law and the English common law, the right to practice medicine and surgery was free to all persons.- It is therefore not surprising to learn that the barber ^ and the priest * were relied upon to "heal the ill.^' Speculation upon the inadequacy of a government which permitted such a condition receives additional interest in the fact that the barber and priest could not sue and recover for their services — a cardinal privilege of the twentieth century practi- tioner, not only from the standpoint of sustenance, but because a judg- ment in his favor for services rendered is an estoppel to a civil action against him for malpractice; conversely, proof of malpractice is a de- fense to an action for professional services.^ Custom precluded the prac- titioner from making a specific charge for his services, and required him to accept whatever compensation, or Jionorarium, as it was then called, his patient chose to pay. The inevitable result of the conditions fostered by these customs prompted Parliament to pass a statute during the reign of Henry V. (1422), which, under a penalty of both line and imprison- ment, prohibited anyone "using the mysterie of physyck unless he hath studied in some university and is at least a bachelor of science." The Medical Profession Established. — Following this legislation by ^See Com. v. Gibson, 7 Pa. Dist. Eep., 386; Com. v. Finn, 11 Pa. Sup. Ct., 620; Matter of Campbell's Registration, 197 Pa., 581; Dent v. W. Va., 129 U. S., 114; Eeetz V. Mich., 188 U. S., 505. ''Benton v. State, 21 Neb., 445; State v. Morrill, 7 Ohio Dec, 52; State v. Carey, 4 Wash., 424. ^Allison V. Haydon, 4 Bing., 619. On the low state of surgery in the Middle Ages, see Kottelmann: " Gesundheitspflege in Mittelalter, " 1890, 216. * Baas : ' ' Geschichte der Medicin, ' ' 204 ; von Raumer : ' ' Hohenstauf en, ' ' 6, 438; Fort: "History of Medical Economy During the IVIiddle Ages," 1883, chaps, xiii and xviii. ^Abbott V. Mayfield, 8 K^n. App., 387. 678 ANESTHESIA Parliament, the practice of medicine savored of a profession; but it was not until Parliament enacted the well-known act of Henry VIII. / which denounced the medical profession as "ignorant persons who could tell no letters on the book, common artificers, smiths, weavers, and women, who took upon themselves great cures, partly using sorcery and witchcraft, and partly applying very noxious medicines to the disease," that it became a well-defined and established profession. With this cloak of legislative protection thrown around it, the profession at once at- tained a higher standard; medical schools were organized and various systems of medicine came into existence. Contest Between the Schools of Medicine. — The greater amount of subsequent legislation in both England and America, between 1550 and 1890, grew out of the jealousy existing between the followers of such schools as Allopathy and Homeopathy. It is indeed a curious com- mentary on the history of the medical profession that the enmity be- tween the several schools and systems, growing out of the efllorts of one to fortify itself by legislation at the expense of loss of privilege to the other, was reflected in the legislature of the State of New York during the latter half of the nineteenth century, when, in its efforts to appease the warring schools, it enacted laws so liberal that the doors of the medi- cal profession were opened to ignorant, and even fraudulent, empirics — a condition which happily has been remedied by more recent legisla- tion. The Status of the Physician. — The legal status of a physician is frequently compared to that of the lawyer, but there is one important element which differentiates the two professions and should be con- stantly borne in mind in any comparison; the lawyer is an officer of the Court, and, because of this relation, the Court has summary power to inquire into his professional conduct in connection with any case; whereas the physician is under no such restraint, and the medical so- cieties, which have been organized for the purpose of protecting the public against imposters, frequently find this power so limited that it often becomes necessary for the public to resort to the legislature for protection. The status of a physician in this country was ably de- scribed by the late Justice Pield, in delivering the opinion of the Su- preme Court of the United States affirming the constitutionality of the legislation prescribing the qualifications of one to practice medi- cine:^ "Few professions require more careful preparation by one who seeks to enter it than that of medicine. It has to deal with all those subtle and mysterious influences upon which health and life depend, and requires not only a knowledge of the properties of vegetable and ''3 Henry VIII., c. 11; 14 and 15 Henry VIII. 5; 5 Car., 1. "Bent V. West Virginia, 129 U. S., 114, affirming 25 W. Va., 1. For the med- ical practice laws of all States, see "American Medical Directory," 3rd ed., 1912. THE MEDICO-LEGAL STATUS OF THE ANESTHETIST 679 mineral substances, but of the human body in all its complicated parts, and their relation to each other, as well as their influence upon the mind. The physician must be able to detect readily the presence of disease, and prescribe appropriate remedies for its recovery. Everyone may have occasion to consult him, but comparatively few can judge of the qualifications of learning and skill which he possesses. Keliance must be placed upon the assurance given by his license, issued by an authority competent to judge in that respect, that he possesses the requisite qualifications. Due consideration, therefore, for the protec- tion of society may well induce the State to exclude from practice those who have not such a license or who are found upon examination not to be fully qualified. The same reasons which control in imposing con- ditions, upon compliance with, which the physician is allowed to prac- tice in the first instance, may call for further conditions as new modes of treating disease are discovered, or more thorough acquaintance is obtained of the remedial properties of vegetable and mineral substances, or a more accurate knowledge is acquired of the human system and of the agencies by which it is affected. It would not be deemed a matter for serious discussion that a knowledge of the new acquisitions of the profession, as it, from time to time, advances in its attainments for the relief of the sick and suffering, should be required for continuance in its practice, but for the earnestness with which the plaintiff in error insists that, by being compelled to obtain the certificate required, and prevented from continuing in his practice without it, he is deprived of his right and estate in his profession without due process of law. We perceive nothing in the statute which indicates an intention of the legislature to deprive one of any of his rights/' The wisdom underlying the statutes requiring a general education as a prerequisite, supplemented by special study at accredited medical schools, as qualifications precedent to the application for the license to practice medicine, cannot be questioned. The legislation of the sev- eral States of the United States in this respect has been approved by the courts in holding those statutes constitutional which prohibit the practice of medicine and surgery by unlicensed persons.^ On the other hand, when the licentiate has conformed to these reasonable require- ments, it follows that it is the better part of wisdom to rely on his integrity ~ and desire to succeed in the application of his knowledge, skill, and judgment, thereby characterizing his profession Avith little restraint in the fields of experiment and investigation; for to limit the ^BlalocJc V. State, 112 Ga., 338; 'Conner v. State, 46 Neb., 157; State v. Mylod, 20 E. I., 632; State v. Van Doran, 109 N. C, 864; Hale v. State, 5S Ohio St., 676; State v. Carey, 4 Wash., 424. ^ That a State may require good character on the part of the licentiate : Hawker v. Netv York, 170 U. S., 189. 680 ANESTHESIA latitude, os it were, of his independence of thought, obviously would be tantamount to impeding progress in both the art and science of medicine. By the same token, it is impossible to prescribe a fixed rule of responsibility on the part of the practitioner, inasmuch as the cir- cumstances and conditions surrounding cases vary, and accordingly all conclusions with respect to a physician's liability must be drawn from the facts underlying each particular case. It is upon this theory that the courts have held that the defendant cannot successfully meet the charge of malpractice by showing his methods were successful in simi- lar cases.^ THE PHYSICIAN'S LIABILITY Ethical Liability of the Physician. — While the privilege which permits the lips of the physician to remain sealed and to hold inviolate the relations between physician and patient has its foundation in the civil resi^onsibility of the physician to inform himself of the habits, tendencies, circumstances, and history of the patient,^ it is to that higher law, the ethics of the medical profession, that society must ultimately ^ Baker v. Hancock, 63 N. E., 323; 64 N. E., 38; but see Stern v. Laning, 106 La., 738. ^ Communications from a patient to his physician were not privileged at com- mon law: Eex v. Gibbons, L. C. and P., 97; Broad v. Pitt, 3 C. and P., 518; God- dard v. Gardner, 28 Conn., 172; Barnes v. Harris, 7 Cush. Mass., 577; People v. Stout, 3 Park. Crim. N. Y., 670 ; Kendall v. Grey, 2 Hilt. N. Y., 300 ; but on con- siderations of public policy: Lissak v. Crocker, 119 Cal., 442; Kling v. Kansas City, 27 Mo. App., 231; Boyt v. Hoyt, 112 N. Y., 493. Statutes have been enacted in most jurisdictions prohibiting the disclosure, against the will of the patient, of information acquired by physicians in their professional capacity: Conn. Mut. L. Ins. Co. v. Union Trust Co., 112 U. S., 250; Dreier v. Cont. L. Ins. Co., 24 Fed. Eep., 670; Shafer v. Eau Claire, 105 Wis., 239.; Wells v. N. E. Mut. L. Ins. Co., 187 Pa St., 166; Davis v. Swpreme Lodge, etc., 165 N. Y., 159; Territory v. Corbett, 3 Mont., 50; Blair v. Chicago, etc., 89 Mo., 334, 383 ; Cooley v. Foltz, 85 Mich., 47 ; Nelson v. Niederland Co., 110 Iowa, 600; Bower v. Bower, 142 Ind., 194; and Colo. Fuel Co. v. Cummings, 8 Colo. App., 541. In the case of Robinson v. Swpreme Commandery, U. C. G. C. of W., 79 N. Y. S., 13, it was stated that Code Civ. Proc., 834, provides that physicians shall not be allowed to disclose information acquired in attending a patient in a professional capacity. An Indiana statute provides that a physician shall be incompetent to testify, over his patient's objections, as to any knowledge acquired by him in treating such patient: Aspy v. Botkin, 66 N. E., 462. Utah Eev. St., 3414, provides that a physician cannot, without the consent of his patient, be ex- amined in a civil action as to any information acquired in attending the patient which was necessary to enable him to prescribe for the patient. In order that such statutes may apply, it is necessary that the relation of physician and patient should exist or at least that conditions are such that the patient is impressed with the belief that it does: People v. Koerner, 154 N. Y., 355; Clarke v. State, 8 Kan. App., 782. THE MEDICO-LEGAL STATUS OF THE ANESTHETIST 681 look for protection rather than to legislatures and courts. The sanc- tity of the relations between physician and patient has ever been held with a most profound appreciation throughout the history of the medi- cal profession; and in this respect the comprehensive ethical code at- tributed to Hippocrates admits of no amendment. The Civil Liability of the Physician. — In defining the necessary qualifications on the part of the practitioner, the courts have held, with- out exception, that one holding himself out to the public as a general practitioner of medicine and surgery must possess and exercise the average degree of skill and learning possessed by members of the pro- fession practicing in similar localities,^ in the light of the present state of medical science.^ The physician is not infallible, and, except by ex- press agreement, in accepting a case, does not guarantee a cure.^ The reasonable and ordinary care, skill, and diligence demanded by this rule, are those which are commonly practiced by physicians and surgeons in the same, or similar, localities and in the same general line of practice in similar cases. The degree of care, skill, and diligence varies in differ- ent communities ^ and in different cases. The opportunity for observ- ing the latest approved methods of treatment, and the facilities for obtaining drugs and appliances, are material in determining the re- sponsibility on the part of the practitioner; hence, it will be seen that the above rule exacts higher degrees of care, skill, and diligence on the part of the city practitioner, than is demanded of the practitioner in the more remote communities. "^ Pike V. Honsinger, 155 N. Y., 201; Eislein v. Palmer, 7 Ohio Dec, 365; Lawson v. Comnaway, 37 W. Va., 159; Nelson v. Harrington, 72 Wis., 591; Mullin V. Flanders, 73 Vt., 95; Jackson v. Burnham, 20 Colo., 532; and Force v. Gregory, 63 Conn., 167. Not in "his locality": Whitesell v. Hill, 101 Iowa, 629; Burk v. Foster, 24 Ky. Law Rep., 791; 114 Ky., 20. Cf. 53 Neb., 28; 92 N. Y. S., 1063; and 37 W. Va., 159, wherein "his community" is specified. In Wohlert v. Seihert, 23 Pa. Super. Ct., 213, the comparative distinction is "the skill . . . ordinarily pos- sessed by the average of members of the profession in good standing. ' ' " Baker v. Hancock, 63 N. E., 323 ; 29 Ind. App., 456 ; 64 N. E., 38 ; Thomas V. Dabblemont, 67 N. E., 463; 31 Ind. App., 146; Dunbauld v. Thompson, 80 N. W., 324; 109 Iowa, 199; Forrell v. Ellis, 105 N. W., 993; 129 Iowa, 614; Gil- lette V. Tucker, 65 N. E., 865; 67 Ohio St., 106; 93 Am. St. Eep., 639; Bigney v. Fischer, 59 A., 72; 26 E. I., 402; and Eislein v. Palmer, 7 Ohio, Dec, 365. On the implied undertaking of a physician, see also Eich v. Pierpont, 3 F. and P., 35; Pettigrew v. Lewis, 46 Kan., 78; Small v. Howard, 128 Mass., 131; Pike v. Hon- singer, 155 N. Y., 203; McCandless v. McWha, 22 Pa. St., 261. In the last case it was stated that the care, skill, and diligence exercised must be that of "thor- oughly educated" physicians, but it was evidently not intended to impose a higher standard of care than that usually required. See Smothers v. Hanks, 34 Iowa, 286. ' Ewing v. Goode, 78 P., 442 ; Dye v. Corbin, 59 W. Va., 266. * Whitesell v. Hill, 70 N. W., 750. 682 ANESTHESIA Malpractice. — The failure on the part of the practitioner to exer- cise "the average degree of skill and learning possessed by members of the profession practicing in similar localities, in the light of the present state of medical science," resulting in injury to the patient, is malprac- tice, and renders the practitioner liable for the injuries resulting there- from.^ However, a mere error in judgment does not constitute mal- practice, unless such error is inconsistent with the degree of skill which it is the duty of a physician to possess. In a leading case the Court has said : ^ "The law relating to malpractice is simple and well settled, although not always easy of application. A physician and surgeon, by taking charge of a case, impliedly represents that he possesses, and the law places upon him the duty of possessing, that reasonable degree of learning and skill that is ordinarily possessed by physicians and sur- geons in the same or similar locality where he practices, and which is ordinarily regarded by those conversant with the employment as necessary to qualify him to engage in the business of practicing medicine and surgery. Upon consenting to treat a patient, it becomes his duty to use reasonable care and diligence in the exercise of his skill and the applica- tion of his learning to accomplish the purpose for which he was employed. He is under the further obligation to use his best judgment in exercising his skill and applying his knowledge. The law holds him liable for an in- jury to his patient resulting from want of the requisite knowledge and skill, or the omission to exercise reasonable care, or the failure to use his best judgment. The rule in relation to learning and skill does not require the surgeon to possess that extraordinary learning and skill which be- long only to few men of rare endowments, but such as are possessed by the average number of the medical profession in good standing. Still he is bound to keep abreast with the times, and a departure from approved methods in general use, if it injures the patient, will render him liable, however good his intentions may have been." The failure on the part of the patient to follow the reasonable and necessary instructions of the physician relieves him of responsibility.^ Similarly, a physician is under no legal obligation to accept a case against his will; but, having accepted, he cannot withdraw without ^ But a mere want of due care and skill gives no right of action when no injury has resulted : Swing v. Goode, 78 Fed. Rep., 442 ; Cay ford v. Wilbur, 86 Me., 414 ; Bowe V. Lent, 42 N. Y., 483 ; Fowler v. Sergeant, 1 Gant. Cas. Pa., 355. ^ Pike V. Eonsinger, 155 N. Y., 201. On a physician's liability for errors of judgment, see also Carpenter v. BlaTcer, 50 N. Y., 696; Heath v. Glisan, 3 Or., 64; McEee v. Allen, 94 111., App., 147. As to what constitutes negligence or malprac- tice, see Sullivan v. McGraw, 118 Mich., 39; Keller v. Lewis, 65 Ark., 578. ^ Geiselman v. Scott, 25 Ohio St., 86 ; Becker v. Janinski, 27 Abb. Cas. N. Y., 45; Haire v. Eeese, 7 Phila., 138; Haering v. Spicer, 92 111. App., 449; DuBois v. Decker, 130 N. Y., 325. For contributory negligence on the part of patient: Haering v. Spicer, 92 111. App., 449. THE MEDICO-LEGAL STATUS OF THE ANESTHETIST 083 giving reasonable notice/ and the fact that his services are gratuitous does not relieve him of the responsibility to exercise reasonable and ordinary care, skill, and diligence. He is civilly responsible for the want of skill and negligence on the part of his partners, agents, ap- prentices, and assistants/ and, while he incurs no liability in the failure to effect a cure,^ in case he doubts his competency in a particular case it is both his legal and moral duty to recommend the employment of another physician.* The physician is under an implied obligation, when he undertakes a case, to bring to his assistance such obtainable remedies and appliances as discovery and experience have found to be most proper and beneficial, and which are therefore sanctioned by use in such cases ; ^ but the mere fact that the instrument used is unusual is not sufficient to show a want of care and skill. ^ The practitioner is chargeable with a knowledge of the probable consequences of an injury or of negligence or unskilfulness / he is bound also to know the natural and probable results of the remedy he uses ; ^ and, in order to be relieved from liability on the ground that his course was pursued through an error of judgment, he must keep within recognized and approved meth- ods, and cannot depart from the known rule and usage of the profes- sion to ramble in the fields of investigation and experiment." Finally, it should not be overlooked that it is the duty of the physician to in- form himself of those habits, tendencies, and circumstances of the pa- ^ On the liability of a physician for failure to attend a patient, see Dale v. Lumber Co., 48 Ark., 188; Mucci v. Houghton, 89 Iowa, 608; Barbour v. Martin, 62 Me., 536; Gerlcen v. Plimpton, 70 N. Y. S., 793; 62 App. Div., 35; Lathrope V. Flood, 63 Pac, 1007. On the physician's right to determine the frequency of his visits to a patient, see 51 L. E. A., 298. ^ Tish V. Welker, 5 Ohio Dec, 725; Willcins v. Ferrell, 10 Texas Giv. App., 231. ^Physicians are not insurers of successful or beneficial results: Swing v. Goode, 78 Fed. Eep., 442; Styles v. Tyler, 64 Conn., 432; Tish v. Welker, 7 Ohio N. P., 472; McKee v. Allen, 94 111. App., 147; English v. Free, 205 Pa., 624. *See Mallen v. Boynton, 132 Mass., 443. ^Stevenson v. Gelsthorpe, 10 Mont., 563; McCandless v. McWha, 22 Pa., 261. 'Alder v. Buckley, 1 Swan Tenn,, 69; Prichard v. Moore, 75 111. App., 553. It has been ruled in Missouri (Vanhooser v. BergTioof, 90 Mo., 487) that whether or not the practitioner in substituting other appliances for those which had been properly tested and were commonly used was guilty of a want of the requisite degree of care and skill is a question for the jury. This decision is of particular interest to the anesthetist, since the development of anesthetic apparatus is progressive, and the introduction of novel appliances is largely due to indi- vidual effort and experience. ' Gerken v. Plimpton, 62 N. Y. App. Div., 35; Dubois v. Decker, 130 N. Y., 325. ^ Bogle V. Winslow, 5 Phila., 136; 20 Leg. Int., 46. » Slater v. Baker, 2 Wils. C. PL, 359 ; Jackson v. Burnham, 20 Colo., 532 ; Teffi V. Wilcox, 6 Kan., 46; Branner v. Stormont, 9 Kan., 51; Patten v. Wiggin, 51 Me., 594; Hesse v. Knippel, 1 Mich. N. P., 109; Pike v. Honsinger, 155 N. Y., 203. 684 ANESTHESIA tient which are necessary and relevant in the prudent management of the case. Liability of the Specialist. — If the specialist professes to belong to a particular school of practitioners/ he must measure up to the stand- ard of that school/ for "the law implies that surgeons and physicians, in the treatment of all cases they undertake, should exercise reasonable care and diligence, and should give attention proportionate to the deli- cacy of the operation and case." It is upon this theory that if a physician holds himself out as hav- ing special knowledge and skill, "he is bound to bring to the discharge of his duty to a patient employing him as such specialist not merely the average degree of skill possessed by general practitioners, but that special degree of skill and knowledge possessed by physicians who are specialists in such cases, in the light of the present state of scientific knowledge,^ for, obviously, to measure the liability of a specialist by the standard appliable to the ordinary family physician, would open the door of the medical profession to quackery and permit consequent fraud upon the public. In defining the responsibilities of a specialist, a Court* has well said: "The question when a physician becomes a specialist is not one of law, but one of fact primarily for his own determination; but, when he holds himself out as a specialist, it becomes his duty to use that de- gree of skill which such a practitioner of necessity should possess." The reasoning in this opinion is not predicated upon any new theory, nor in its application is it peculiar to the relations between physician and patient, for it is a well-established principle of law that, "in all those employments where peculiar skill is requisite, the one who offers his services is understood as holding himself out to the public as possessing the degree of skill commonly possessed by others in the same employment." With respect to the degree of skill required by anesthetists, the de- cisions pertaining to specialists^ fortify the conclusion that the anes- thetist should be held to that degree of care, skill, and knowledge ordi- narily possessed by practitioners in good standing devoting special at- tention and study to the administration of anesthetics. As a rule, the surgeon is responsible to the family, while the anesthetist is responsible to the surgeon; but if the anesthetist has been specially called in by ^ Force v. Gregory, 63 Conn., 167; Bowman v. Woods, 1 Greene Iowa, 441; Corsi V. MaretseTc, 4 E. D. Smith, N. Y., 1; Williams v. Poppleton, 3 Or., 131; Hesse v. Enippel, 1 Mich. N. P., 109. ° Martin v. Courtney, 77 N. W., 813. ^ Baker v. Hancock, 63 N. E., 323; 64 N. E., 38; S9 Ind. App., 456. * Baker v. Hancock, 63 N. E., 323. ^ Feeney v. Spalding, 89 Me., Ill; McMurdock v. Kimberlin, 23 Mo. App. 523; Stern v. Lanng, 106 La., 738. THE MEDICO-LEGAL STATUS OF THE ANESTHETIST 685 the patient or the practitioner, he is on the same footing as the surgeon. The Criminal Liability of the Physician. — The criminal liability on the part of a physician, for the purposes of this discussion, may be summarized in the following propositions: (1) Where the practitioner wilfully adopts procedure liable to jeopardize the life or health of the patient.^ (2) Where the practitioner wilfully omits to adopt the procedure necessary in safeguarding the life or health of the patient. ^ (3) Where injury to the patient results from gross ignorance or negligence on the part of the physician. (4) Where the practitioner is guilty of conduct prohibited by statute. Xo application of the above propositions to procedure on the part of the practitioner can be made without due regard to the principle of law that one is presumed to intend the natural, necessary, and probable consequence of his acts. Gross Ignorance or Negligence. — The liability on the part of the practitioner growing out of gross ignorance or negligence is of serious concern to the anesthetist in view of the occasional deaths which occur during and immediately subsequent to an anesthetization. It is a monument to the honor of the American medical profession that so few cases have grown out of the liability of the practitioner for death resulting from gross ignorance or negligence in the adminis- tration of anesthetics that the law in this country cannot be said to be clearly defined. In general it may |)e said that the law presumes that the practitioner has used due care and skill, and accordingly the burden of proof is on him who alleges gross ignorance or negligence.^ This presumption re- quires the plaintiff in civil actions to prove his case by a preponderance of evidence and in criminal cases beyond a reasonable doubt. The few American decisions read in the light of the English law ^ For a discussion of the question, ' ' Has the Physician Ever the Eight to Ter- minate Life?" see 55 Albany Law J., 136; and Haeckel: "Wonders of Life," 1905, 116. ^ Where the death of a person results from the criminal negligence of the prac- titioner in the treatment of a case, the latter is guilty of manslaughter: State v. Eeynolds, 42 Kan., 320; Uyatt v. Adams, 16 Mich., 198; State v. Gile, 8 Wash., 12. The real question upon which criminal liability depends is whether there was criminal negligence, which is hardly a matter of degree. On the facts con- stituting criminal negligence, sec State v. Hardister, 38 Ark., 605; Com. v. Pierce, 133 Mass., 165 ; Bex v. Long, 4 C. and P., 398 ; WeM 's case, 2 Lewin C. C, 196 ; and Beg. v. Chamberlain, 10 Cox C. C, 486. ' Pettigretv v. Lewis, 25 Pac. E., 458 ; Feeney v. Spalding, 80 Me., 111. ; FecTc v. ButcMnson, 55 N. W., 511; Wohlert v. Siehert, 23 Pa. Super., 214; Georgia North- ern By Co. V. Ingram, 40 S. E., 708. 686 ANESTHESIA indicate that the courts, in ascertaining the responsibility of the prac- titioner when death has resulted from the administration of anesthetics, consider three classes of facts, viz.: (1) the necessity of the operation; (3) the competency of the operator; (3) whether the wound or injury would have proved mortal without the operation. Among the pertinent inquiries which arise in determining gross ignorance or negligence under this classification of facts are the kind and fitness ^ and quality of the anesthetic administered, the method of administration followed, the consent ^ of the patient to its administra- tion, the peculiar condition or temperament of the patient, if necessary and relevant, and the circumstances permitting of their acquirement,^ skill in the use of instruments, and proper qualifications * of and in- structions to those in immediate charge of the patient as to the use of medicines,^ a disregard of which by the practitioner, if found gross, renders him criminally responsible. Hence, it will be seen that criminal malpractice in this respect differs from civil malpractice only in degree. In defining criminal malpractice in a leading case, the Court said:^ '^Criminal negligence exists where the physician or surgeon, or per- son assuming to act as such, exhibits gross lack of competency, or gross inattention, or criminal indifference to the patient's safety, and this may arise from his gross ignorance of the science of medicine or surgery and of the effects of the remedies employed, through his gross negligence in the application and selection of remedies and his lack of proper skill in the use of instruments, or through his failure to give proper instructions to the patient as to the use of the medicines." It is important to mention here that it has been held by the Supreme Court of Vermont that a physician administering an anesthetic is not liable for not protesting against an operation not favored.'^ Statutory Liability. — To determine the statutory liability on the part of the practitioner, it is necessary to examine the statutes of the several States. As indicated above, they have their origin in the police power of the State. Other than those statutes which prohibit the per- '^ Bogle V. Winslow, 5 Phila. Keports, 136. ^ Mehr v. Williams, 95 Minn., 261. Actions have been brought in England for- alleged anesthetization without consent. In these cases, the patient and anesthet- ist, who was also the operator, were alone together ; but they failed on the grounds that anesthetization by force was impossible and that there was collateral evi- dence of consent. For discussion of consent from an English anesthetist 's point of view, see J. D. Mortimer: "Anesthesia and Analgesia," 1911, 255. ^ Lewis V. Dwinel, 84, Me., 497; Logan v. Field, 75 Mo. App., 594. * For qualifications of a trained nurse, see Art. 12, Public Health, Law, State of New York, 1909. ^ Kampton v. State, 50 Fla., 55. ° Hampton v. State, 39 Southern E., 424. '75 Atl. Eept., 641. THE MEDICO-LEGAL STATUS OF THE ANESTHETIST GS7 formance of illegal operations ^ and the treatment of a patient by a physician under the influence of intoxicants, with the exception of Ohio, which prohibits the administration of anesthetics except in the presence of a third party who must be a competent witness,^ none of the States has passed statutes directly affecting the anesthetist. An anesthetic should not be administered without the presence of an as- sistant or a third person, except in cases of emergency; and, in the ab- sence of a professional assistant, the operator must assume the entire responsibility. If, however, the assistant is duly licensed, the responsi- bility is assumed by both. Finally, it may be said that, in the administration of anesthetics, whether by physician, surgeon, dentist, anesthetist, or other professional assistant, the practitioner should at all times exercise the highest de- gree of caution, for it is not only difficult to determine the proximate cause of death in cases where an anesthetic has been used, but women, particularly young women, are likely to have erotic sensations while under its influence, and thus an added responsibility may be brought to the practitioner in defending his good character and fidelity of pur- pose.^ 1 No one may give an anesthetic for an illegal operation. 2 ' ' Whoever uses upon another an anesthetic, unless at its administration, and during the whole time the person is v^holly or partly under the direct influence of it, there is present a third person competent to be a witness, shall be fined not more than Twenty-five Dollars nor less than Five Dollars" (Laning's "Rev. Stat.," 10685). 3 Sexual intercourse with a woman while she is unconscious has been held to be against the will of the woman and without her consent so as to constitute rape : Com. V. Burke, 105 Mass., 377; Com. v. Childs, S Pgh., 398; Lewis v. State, 30 Ala., 54; Shirwin v. People, 69 111., 55. An attempt to administer chloroform to a woman for the purpose of having sexual intercourse with her while she is under its influence is an attempt to rape: Milton v. State, 2i Texas App., 284. As to chloroform as a means of facilitating crime, see Vroc. N. ¥. Med. Leg. Sac, 1872, 298-317; cf. also Sogers v. State, 33 Ind., 543. However, in an interesting pamphlet by Stephen Rogers on chloroform (Har- per and Bros., New York, 3877), it is argued with much force that for the pur- poses of attack chloroform cannot be effectively used. See also: 3 Whart. and St. Med. J., 245, 594; and Wharton's "Criminal Law," 1896, 1, 527. But cf. Ford V. State, 41 Tex. Crim., 270; State v. Greene, 2 Ohio Dec, 255; 2 West. L. Month., 185. For cases of conviction for rape committed on a woman under the influence of ether, see State v. Green, 3 Whart. and St. Med. J., 597; and Com. v. Beale, ibid., 245, 596, 612. On alleged murder by inhalation of chloroform to sleeping unconscious victim, see Fairchild: Medico-Legal J., 24, 19, 34. For a discussion of the question, "Can Chloroform Be Used by Inhalation to Commit Murder, Robbery or other Crime on an Unconscious Victim," Bell: Medico-Legal J., 24, 28. On "The Medico-Legal Questions Arising in the Case of Patrick," Bell: Medico-Legal J., 22, 494, 529. CHAPTEE XX A LIST OF ANESTHETICS 1 Including General Anesthetics, Local Anesthetics, and Anesthetic Mix- tures, Both Past and Present, With Synonyms While local anesthetics may be regarded as nothing more than strong hypnotics, so far as possible anesthetics have been carefully discrim- inated from hypnotics. However, hypnotics employed as adjuvants have been included. Anesthetic sequences are not included, except in exceptional cases, as, for example, those not referred to- elsewhere in the text of this work. Such substances as atropin, phenylacetyl, homatropin, ortho-chlor-cocain, • meta-nitro-cocain, vanillin, piperonal, etc., which have little or no pro- nounced anesthetic action, or whose anesthetic action is obscure, and which have never been employed in practice for the production of an- esthesia or whose effects have never been the cause of complaint among workmen in industries, are not considered. While the effects of some of the many dental anesthetics may be due, at least in part, to the re- sults of pressure, yet the authors have adhered to the plan of present- ing a full and complete list of these. The preparations termed "eye drops" have been, in general, omitted. A. C. E. Mixture. — A mixture of A(lcohol), C(hloroform), and E(ther), intended for a safer and quicker anesthetic than either in- gredient alone. The theoretical neutralization of the bad effects of the one anesthetic by the good effects of the others and an intensifying of the anesthetic qualities have not been realized in practice. ^ In the Am. Drug, and Fharm. Bee, Feb. 13 and 27, and Mar. 13, 1911, one of the authors (C. B.) published "A List of Anesthetics"; but a number of omissions occurred in this very brief paper, and the insertions necessitated for completion of the list, together with fuller descriptive matter and bibliographical data, are included here. The plan has been to present a complete list of all anesthetics, both past and present; consequently, by no means all mentioned are in use or on the mafket. A number of preparations which include anesthetics in their composition are given. The authors are indebted to a number of manufacturers for information con- cerning their products; but, wherever possible, the information presented has been taken from the literature. We are especially grateful to Dr. Eobert H. Ferguson for helpful suggestions. 688 A LIST OF ANESTHETICS 689 Mixtures began with Pitha to be used in 18G1 (Wiener med. Woch., 1861, 25 and 26). In England, George Hartley is said to have used them and to have introduced the alcohol before 1864. He proposed the A. C. E. Mixture, now commonly known, which is often referred to as the L. M. & C. S. (London Med. and Chir. Soc.) Mixture, since this society investigated and recommended it in 1864 (Med.-Chir. Trans., London Med. and Chir. Soc, ^7, 341, 342). As defined by them it consists of: Alcohol (sp. gr., 0.838), 1 part; Chloroform (sp. gr., L497), 2 parts; and Ether (sp. gr., 0735), 3 parts. Mix. For other combinations of alcohol, chloroform and ether, see Martin- dale's Mixture, Eeyne's Anesthetic Mixture, Billroth's Mixture, Nuss- haum's Mixture, Bicliardsons Mixture, Vienna General Hospital Mix- ture, and Vienna Anesthetic. Acetaldehyd. — Poggiale found aldehyd to be a prompt and ener- getic anesthetic, but Simpson stated that it produced irritation and dyspnea. Francis and Fortescue-Brickdale ("The Chemical Basis of Phar- macology," 1908, 107) state that in acetaldehyd "the anesthetic prop- erties are more marked (than in formaldehyd), and still more pro- nounced in its polymeric form paraldehyd, which is not so toxic as metaldehyd." See Paraldehyd. Acetic Ether. — See Ethyl Acetate. Acetofonn.— Acetoform is a brand name for acetone-chloroform. Acetoform dusting-powder consists of acetoform 1 part and boric acid 47 parts. See Chloretone and Methaform. Acetone. — Acetone (Dimethylketone; Dimethylketal ; Ketopropane; Methylacetyl ; Pyroacetic Ether), CH3.CO.CH3, produces intoxication and sleep; it is, however, less powerful in action than ethyl ether or chloroform, and is less toxic than ethyl alcohol. It possesses anesthetic properties. See Propion. Acetone-Chloroform. — See Chloretone and Methaform. ■ Acetylene. — One per cent of acetylene in air is said to produce nar- cosis with failure of heart and respiration. Lauder Brunton has indi- cated that the characteristic action of aliphatic hydrocarbons, such as acetylene, ethylene, propylene, butylene, amylene, etc., is on the nerve centers, tending to produce first excitement and then narcosis; they act on the sensory side. On the other hand, the aromatic hydrocarbons (see Benzene, e. g.) act mainly on the motor side, producing convul- sions and paralysis. On these points, see Francis and Fortescue-Brick- dale : "The Chemical Basis of Pharmacology," 1908, 45. 690 ANESTHESIA On the toxicology of acetylene, see Kosemann : Arch. f. exper. Path, u. Pharmacol., 1895, 36; Moissan: Compt. rend., 121; Mosso and Otto- lengui: Rend, della R. Accad. del Lincei, 1896; and Oliver: Brit. Med. J., 1898, 1. Acetylene Dichlorid. — See Dioform. Acetylene Tetrachlorid. — See Tetrachlor ethane. Acidum Amidobenzoicum ^thylatum. — See Anesthesin. Acoin or Acoine (Di-para-anisyl-monophenetyl-guanidin hydro- NH< >0CH,.HC1 chlorid: "Acoine C"/C:N0C,HA A local (dental and oph- NH< >0CH, thalmic) anesthetic, also used in Sehleich's infiltration anesthesia. Acoin is the collective name of the alkyloxy-phenyl-guanidin group of which the hydrochlorid of di-para-anisyl-monophenetyl-guanidin is clinically especially important. Acoine is obtained in the form of a white powder which fuses at 176° F. It is readily soluble in alcohol, and water at 63° F. will dissolve 6 per cent of its weight of acoin. Its solutions are said to be powerful antiseptics and a solution of 0.02 per cent in a nutritive medium will prevent the development of anthrax spores. A 1 per cent solution will not decompose for a long time if kept in a dark place, but should be kept in non-soluble glass. Strong solu- tions of acoin have corrosive properties and consequently are not adapted for subcutaneous or endermal application; a 1 per cent solution or one which is even less concentrated accomplishes anesthesia, and it is said that it can be used without bad results, either immediate or remote. On the anesthetic properties and applications of acoin, see the fol- lowing : Trolldenier: Therap. Monatsh., 1898, No. 1, 36. Guibert: Clin. Ophthal., 1899, No. 17. Darier: Clin. Ophthal., 1899, No. 12. Hirsch : Archiv f. Augenlieil., Jf2, No. 3. Randolph : Ophthal. Rec, Aug., 1899. Carter: Lancet, Oct. 21, 1899. Braun: Kocher's "Enzyklopadie der Chir./' 1900. Trolldenier: Z. f. Thiermedicin, 1901, 80. Stasinski: Therap. der Gegenwart, 1901, No. 5. Senn, Schw. : Yrtljschr. f. Zahnheil., 10, No. 4. Etievant: La Provence Med., Lyon, July 14, 1900. Nipperdey: Deut. Monatschr. f. Zahnheil., Nov. 20, 1902. Spindler: Wratsch. Gaz., 1902, No. 14. Daconto: Deut. Z. f. Chir., 69, 457. Bab : Wiener Zahndrztl. Monatsh., 1902. A LIST OF ANESTHETICS 691 On acoin in combination with cocain ("Acoincocain") as a local anesthetic, see: Darier : "Legons de therapeutique oculaire," Paris, 1902. Kraus: Munch, med. Woch., 1903, 1459. On acoin for purposes of dental surgery, see : Bab : Jour. f. Zahnheilkunde, 1903, No. 1. Simon: Dental Cosmos, Jan., 1904. Krakowski: Subowpatschebny Wjestnik, 1901, No. 8. Acoincocain. — See Acoin. Acoin Oil. — This is a one per cent solution of acoin base in peanut oil and is used principally in eye diseases. Acoinol. — This does not contain acoin hydrochlorid, but 1 per cent of acoin base. Adralgin. — An anesthetic for dental and surgical practice contain- ing thymol, cocain, and adrenalin (epinephrin) in physiological salt solution. This preparation is marketed by a Swiss firm in ampules. Adralgin Chirurgicum. — This contains in 2 c. c. 0.015 gm. thymol- cocain compound and 0.0001 gm. adrenalin. Adralgin Dentale. — This contains 0.01 thymol-cocain compound and 0.000051 gm. adrenalin. Adrenalin and Cocain Tablets. — Each hypodermic tablet contains cocain hydrochlorid 0.01 gm. (1/6 grain) and adrenalin, as borate, 0.0002 gm. (1/300 grain). Esch (Arch. f. e.vp. Path. u. Pharm., 6-^, 84) reported that the addi- tion of adrenalin to novocain, alypin, and especially cocain intensified their local narcotic action. Adrenalin-Kokain-Tabletten. — These small cylindrical tablets con- tain 0.0002 gm. adrenalin and 0.01 gm. cocain hydrochlorid; they are used in dentistry. Adricain. — This is a dental anesthetic tablet containing adrin 1/100 gr. and cocain hydrochlorid 1/10 gr., marketed by a Philadelphia firm. Adrin and Cocain Tablets. — Tablets of epinephrin and cocain. (For dental practice.) Each tablet contains adrin, 0.00065 gm. (1/100 gr.) and cocain hydrochlorid, 0.016 gm. (14 gr.). .ffither Anaestheticus Aranii. — In the chlorination of ethyl chlorid isomers are obtained, and these are also produced in the manufacture of chloral. A variable mixture of the middle members of the series is Liquor Ansestheticus. Another similar mixture, containing the less chlorinated bodies, is the ^ther Ansestheticus Aranii, which boils be- tween -f- 64° and -f- 100° C. The composition of Aran's ether has been CCI3 given as (sp. gr., 1.55 — 1.60; b. p., -1-130° circa); but its CHCL 692 ANESTHESIA composition is very variable and it has been considered unsafe as an anesthetic. It is not used at present. See Lyman's "Artificial Anaes- thesia and Anesthetics," 204. .ffither AnaestheticTis Konig. — A local anesthetic composed of alco- hol-free ether, 1 part, with 4 parts of rhigolene or petroleum ether. .aither Ansestheticus Wiggers. — This anesthetic contains the more highly chlorinated products referred to under ^ther Anaestheticus Aranii, and boils between + 100° and -f 140° C. See Ethyl Cldorid Polychlorated. JEther Chloratus.— See Ethijl Chlorid. ^tho-Methyl. — A mixture of ethyl and methyl chlorids, prepared by a Mayence firm. See Pharm. Ztg., 1ft , 916. .aithoxycaffein. — Used with sodium salicylate (Ceola). ^thoxy- caffeine (CgHg.OCjHg.N^Oa) is obtained by heating monobrom-caf- fein with an excess of alcoholic potassium hydroxid. It forms white or colorless crystals, melting at -|- 140° C, and soluble in hot alcohol and in ethyl ether. The solubility is increased by sodium salicylate. ^thylenum Chloratum. — See EihyUne Chlorid. ^thyliuiii Amidobenzoicum. — An anesthetic. .31thyli-iiin Aminobenzoicum. — See Anesthesin. .ffithyloform. — A mixture of ethyl bromid, ethyl chlorid, and methyl chlorid. Air. — In 1867 an American dentist advertised that he "now takes teeth out painlessly by merely causing the patient to inhale the con- stituents of the atmosphere — oxygen and hydrogen ( !) — chemically combined." (Chem. News, 16, 26.) Mtrous oxid was undoubtedly referred to. Alcohol Phenicum. — See Carbolic Acid. Alcool Trichloramidoethylique. — See Chloralformamid. Allocain. — This is a mixture of novocain and alypin {q. v.), recom- mended, in combination with synthetic suprarenin and thymol, as a local anesthetic in tooth extraction by Proskauer {Z. Zahnheilk., 1911, No. 17). Flury {Z. angew. Chem., 26, No. 35, 242) describes allocain as a mixture of novocain, alypin and adrenalin. Alvatunder. — A local anesthetic said to contain 1 gm. cocain hydro- chlorid, 3 drops of liquid phenol, 3 drops of decolorized tincture of iodin, 10 gm. glycerin, and water to 100 gm. Alypin. — Alypin is 2-benzoxy-2-dimethyl-amino-methyl-l-dimethyl- amino-butane hydrochlorid, CH3.CH2.C(CeH,COO) (CH2N(CH3),). CH,N(CH3)2.HCl=:Ci6H2602N,.HCl. It is closely related to Sto- vain {q. v.). By the action of dichloracetone, CHoCl.CO.CH„Cl, on ethyl-mag- nesium bromid dissolved in ether and decomposition by water of the A LIST OF ANESTHETICS 69^ magnesium compound formed, ethyl-diehlorhydrin, CIl2Cl.C(C.H./) (0H.)CH2C1, is obtained. From this, by the action of dimethylamin, ethyl-tetramethyl-diamino-propanol is produced. This product is treated with benzoyl chlorid and the benzoyl-ethyl-tetramethyl-diamino-pro- panol is neutralized with hydrochloric acid to form the chlorid. Alypin is a white crystalline powder, melting at -J- 169° C. (336.2° F.), hygroscopic and extremely soluble in water. Its solutions are neutral and are not rendered turbid on addition of sodium bicarbonate in moderate quantities, and may be sterilized by boiling for a period not exceeding five minutes, without decomposition. It is easily soluble in alcohol. It has a markedly bitter taste. It should be protected from the air in well-stoppered containers. Two and four per cent solutions are quite stable, but weaker solutions are likely to become mouldy. Addition of potassium iodid test solution to the aqueous solution (1-100) produces a white precipitate; potassium dichromate test solu- tion produces a yellow crystalline precipitate soluble in hydrochloric acid; potassium permanganate test solution produces a violet crystalline precipitate, which turns brown on standing. If 0.1 gm. alypin be mixed with 1 c. c. sulphuric acid and warmed to -(- 100° C. (212° F.) for five minutes and then 2 c. c. water carefully added, the odor of benzoic-ethyl- ester is developed; on cooling, crystals separate out, which are dissolved on adding 2 c. c. alcohol. If alypin is dried at -f 100° C. (212° F.), the loss should not exceed 1.5 per cent. Actions and Uses. — It is a local anesthetic, claimed to be equal to cocain, but not a mydriatic; it is said not to produce disturbance of accommodation and to be less toxic than cocain. It has been highly recommended in ophthalmic practice, and is said to be safe and effi- cient in nose, throat, and ear work, general surgery (spinal analgesia, infiltration anesthesia), and dentistry. Internally it acts as a sedative. With regard to the manner of use, the strengths of solutions employed are about the same as those of cocain. Sterilization may be effected by boiling the required amount of water for ten minutes in a small flask or test-tube stoppered with cotton; alypin is then added and the boiling continued over a small flame for another minute. The solutions should be freshly prepared. Alypin is compatible with alkaline solutions and with suprarenal preparations. According to Schleich, the addition of alypin to cocain in infiltration anesthesia permits of larger quantities of fluid being used, the solutions proposed by him being as follows : (1) Co- cain, 0.1; alypin, 0.1; sodium chlorid, 0.2; and distilled water, 100. (2) Cocain, 0.05; alypin, 0.05; sodium chlorid, 0.2; distilled water, 100. (3) Cocain, 0.01; alypin, 0.01; sodium chlorid, 0.2; distilled water, 100. Dosage. — Externally in the form of a 10 per cent, solution; hypo- 694 ANESTHESIA dermically in 1 to 4 per cent solutions; for the eye in 1 to 2 per cent solutions. As much as 5 c. c. of a 3 per cent solution was well tolerated in one case. Alypin Tablets, 3 1/3 grains. Each tablet contains 0.22 gm. (3 1/3 grains) of alypin. Alypin Tablets, li/s grains. Each tablet contains 0.073 gni. (1% grains) of alypin. Alypin Tablets, % grain. Each tablet contains 0.048 gm. (% grain) of alypin. Alypin Tablets, 1/3 grain. Each tablet contains 0.022 gm. (1/3 grain) of alypin. For further particulars concerning alypin, which has been widely tested therapeutically, consult the following literature, chronologically arranged : Impens: Veut. med. Woch., 1905, 1154. Seifert: Ibid., 1905, No. 34. Stotzer: Ibid., 1905, No. 36. von Kraus: Ibid., 1905, No. 49, 1966. Peckert: Deut. Zahndrztliche Woch., 1905, No. 43, 721. Braun : Deut. med. Woch., 1905, No. 42, 1669. Jakobsohn : Woch. f. Therapie und Hygiene des Auges, 1905, No. 52. Gebb: Aerztl Rundsch., 1905, No. 39. Geth: Dissert. Giessen, 1905. Seeligsohn: Deut. med. Woch., 1905, No. 35. Stephenson: Ophthalmoscope, Nov., 1905. von Sicherer: Ophthal. Klinik, 1905, No. 16. Neustatter: Miinch. med. Woch., 1905, No. 42, 2015. Ohm: Woch. f. Therapie und Hygiene des Auges, 1905, No. 6, 41. Kollner: Berl. Jclin. Woch., 1905, No. 43. Landolt: Woch. f. Therapie und Hygiene des Auges, 9, No. 16, 122. KauflFmann: Aerztl. Eundsc, 1906, No. 9, 97. Steindorff : "Sammelreferat und eigene Beobachtungen," 1906. Sendral: Revue de Therap., 1906, No. 9, 297. Massi : Boll, del Osped. oftalmico di Roma, 1906, No. 1. Kirchner: Ophthalmol. Klinik, 1906, No. 7. Kraus: Miinch. med. Wocli., 1906, No. 29, 1443. True: Revue Generale d' Ophthalmol., Mar. 31, 1906. Darier: CZm. 0^/i^/iaL, 1906, No. 4. Kuoli: Westnih oftalmologie, 1906, No. 6; Petersburger med. Woch., 1906, Eevue No. 8, 25. Weil: Allg. med. Centr.-Ztg., 1905, No. 36. Haass: Woch. f. Therapie und Hygiene des Auges, 1906, No. 50. Zimmermann: Klin. Monats. f. AugenheilTc., 1906, No. 9. Wibo: J. Med. de Bruxelles, 1906, No. 4. .A LIST OF ANESTHETICS 695 Koll: Z. f. drztliche Forthildung, 1906, ISTo. 6. Castresana: Siglo medico, May 16, 1906. Cohen: J. Am. Med. Assn., July 38, 1906. Fischer : Gyogydszat, 1906, No. 7. Baumgarten: Wien. Tclin. liundsc, 1906, No. 36, 676. Finder : .Berl. hlin. Woch., 1906, No. 5, 130. Sternberg: Aerztl. Rundsc, 1905, No. 38. Katz: Deut. med. Woch., 1906, No. 36. Joubeline: Russkij Wratsdt., December 31, 1905; Revue de Therap., 1906, No. 4, 131. Euprecht: Monatssch. f. Ohrenheil., 1906, No. 6. Dold: Korrespond. des wurttemherg. drztl. Landesvereins, 1906, No. 26. Anten: Scapel, 1906, No. 50. Venus: Wiener klin. Rundsc, 1906, No. 51. Eaoult-Pillement : Archiv Internat. de Laryng., Sept., 1906. Freudenthal: Critic and Guide, May-June, 1906. Borszeky: Orvosi Hetilap, 1906, No. 25. Gilles: Zahndrztl. Rundsc, 1906, Nos. 22 and 23. Phillips: Laryngoscope, July, 1906. Dehogues: L'Odontologie, 1906, No. 5. Lohnstein: Deut. med. Woch., 1906, No. 13, 504. Chevallier: Miinch. med. Woch., 1906, No. 14, 683; Klin.-therap. Woch., 1906, No. 12, 282. Mahler: Deut. zahndrztl. Woch., 1906, No. 127. Tauszk: Wiener med. Ztg., 1906, No. 12. Cooper: Denver Med. Times, Nov., 1906. Wanietschek: Prager med. Woch., 1906, No. 50; Allg. med. Centr.- Ztg., 1907, No. 38, 582. Laufer: Reichs-Medizinal-Anzeiger, 1907, No. 17. Borbely: Pester med.-chir. Presse, 1907, No. 31. Shulebin: Mitteil. der militdr-med. Alcad., St. Petersburg, 1907, 176. Biirkner: Berl. klin. Woch., 1907, 389. Euprecht: Monats. f. Ohrenheil., 1907, No. 6. Spira: Die Heilkunde, 1907, No. 9. Kurzwelly: Beitr. z. klin. Chir., 1907, No. 3. Meyer: N. Y. Med. J., Apr. 27, 1907. Dittmer: Monatsh. f. praktische Tierheilk., 1907, No. 5. Frank: Am. J. Ophthal., Nov., 1907. DuFour: Ya. Med. Semi-Month., Jan. 24, 1908. Lewis : J. Am. Med. Assn., May 9, 1908. Bremerman: Surg. Gynec. and Obstet., Nov., 1908. Winslow: Hosp. Bull of Univ. Md., Jan. 15, 1908. 696 ANESTHESIA Gwathmey: Va. Med. Semi-Month., Nov. 13, 1908. Zaun: Milwaukee Med. J., June, 1909. Green: Brit. Med. J., July 34, 1909. Lokey: Atlanta J.-Rec. of Med., July, 1909. Littlejohn : Yale Med. J., Oct.-Nov., 1909. Knight : "Diseases of the Nose, Throat, and Ear," 2nd ed., 1909. Keyes: "Diseases of the Genito-Urinary Organs," 1910. Senator: Miincli. med. WocJi., 1910, No. 10, 534. Bruck : Merck's Reports, 1909, 169. Hamm: Deut. med. Wocli., 1910, No. 35, 1198. Bubenhofer: Munch, med. Woch., 1909, No. 43. Fleissig: Med. Klinik, 1910, No. 5. Eisert: Zahndrztl. Rundsc, 1910, No. 30. Peters: Deut. zahndrzt. Woch., 1910, No. 10. Fischer: Deut. med. Woch., 1910, No. 38, 1759. Barringer: Fol. urolog., Mar., 1910. Goldschmidt : Miinch. med. Woch., 1910, No. 43, 3341. Voigt: Berl. klin. Woch., 1910, No. 46, 3113. Garasch: Wratsch, 1911, No. 33. Eitter: Med. Klinik, 1913, 1336. Euprecht: Monatsh. f. Ohrenheilkunde u. Laryngo-Rhinologie, 1911^ No. 3. Alypin-Gleitmittel. — Tragacanth, 13 gm. ; glycerin, 36 gm. ; mercury oxycyanid, 1 gm. ; distilled water, 370 gm. ; and alypin, 31 gm. Used for anesthetization of the urethra by means of Utzmann's imguent injector. Alypin Nitrate. — Alypin (q. v.) is incompatible with silver nitrate; it is therefore not well adapted for anesthetizing mucous membranes to which silver nitrate is afterward to be applied, since it may to some extent neutralize the effect of the latter through chemical decomposi- tion. Alypin nitrate is said to overcome this difficulty, and it is there- fore recommended in such cases. Its chemical characters, solubility, and strength of solutions are said to correspond essentially to those of aly- pin. It is a white powder, fusing at +159° C, and soluble in water, chloroform, and alcohol. Alypinoids. — Tablets containing alypin and suprarenin, for use in dentistry. Alypin-Tabletten. — 0.03-0.3 gm. alypin, with or without suprarenin borate. See Dolonephran. American Painless Dentists' Anesthetic. — This dental anesthetic is said to contain nitroglycerin, cocain hydrochlorid, morphin hydrochlorid, listerin, and water. Amidin. — See Holocain Hydrochlorid. A LIST OF ANESTHETICS 697 Aminobenzoic Acid Ethyl Ester (Para-). — See Anesthesin. Aminobenzoic Acid Isobutyl Ester. — See Cydoforrn. Aminobenzoyldiethylaminoethanolum Hydrochloricum (Para-) . — See Novocain. Aminocinnamic Acid Alkamine Esters. — These are stated (Meister Lucius and Briining: German Patent 187,593) to have several times the local anesthetic power of those of aminobenzoic acid. Aminocinnamic ethyl ester is said to have met with little success commercially. Ampules Solution Atoxyl, 10 per cent, with Novocain, 1 per cent (Sterilized). — Each 100 c. c. contain: atoxyl, 10 gm., and novocain, 1 gm. (each fluid ounce contains : atoxyl, 48 gm., and novocain, 4 8/10 gm., dissolved in distilled water. Amydricain. — A local anesthetic. Amyl Chlorid. — Richardson (Sci. Am. SuppL, No. 515, 8227) gave the physiological properties of this compound as follows : Odor of vapor slightly pungent. Quantity of fluid required for complete anesthesia, 6 to 8 fluid drachms. Required charge of air, 10 per cent. Action slow, with very slight rigidity in second stage. Anesthesia extremely profound and prolonged. Animal temperature much reduced. Re- covery rapid when it commences. Vomiting frequent. The great peculiarity in the action of amyl chlorid is in the reduction of animal temperature. In one instance recorded by Richardson, in a rabbit, the temperature fell from -)- 103° F. to -f- 83° F., yet perfect recovery, in warm air, followed. According to the same authority, the anesthesia is too slow and profound for ordinary practice, but might be valuable for reduction of high febrile temperatures. After death, cardiac action is long persistent; the blood is fluid, but of natural color on both sides. The red corpuscles are shrunken and elongated, with truncated ends, some stellate. The brain is left bloodless and of purest white. Amyl chlorid was introduced by B. W. Richardson in 1869. Amyl Hydrid.— This compound, introduced as an anesthetic by J. Bigelow and B. W. Richardson in 1867, has, according to the latter (Sci. Am. Suppl., No. 515, 8227), the following physiological prop- erties : Vapor odorless and free from pungency. Quantity of fluid re- quired, 6 to 12 fluid drachms for complete anesthesia. Required charge of air by vapor, 40 per cent. Anesthesia is very rapid, being profound in two minutes, with a short period of spasmodic movements. Recovery is very rapid, without vomiting, and the temperature of the body is un- changed. According to Richardson, the anesthetic action is extremely rapid, but dangerous, probably from the insolubility of the vapor in the blood. The heart is easily paralyzed, but irritability of the voluntary muscles is long retained. See Hydramyl and Pentene. 698 ANESTHESIA On death from the inhalation of a mixture of ether and amyl hy- drid, see Hardie, Lancet, April, 1875. Amyl Nitrite (Isoamyl Nitrite). — Amyl nitrite was first brought into notice by Guthrie in 1859, and was made the subject of investiga- tion by Eichardson in 1863-5 and 1870; by Eutherford, Gamage, and Brunton in 1869 ; by Wood in 1871, by Landendorf in 1874, by Bourne- ville in 1875, and at various times by a number of other investi- gators. Eichardson states that amyl nitrite is absorbed by the bodies of animals, however introduced. The effects of the compound are most conspicuous upon the motor apparatus of the body, especially upon the vascular motor apparatus. Its effects upon the power of sensation are not as early apparent; hence it is often considered to be devoid of anesthetic properties. Consciousness, however, may disappear before death from its use. Brunton believed that amyl nitrite diminished the blood pressure by a local effect upon the walls of the smaller arteries. Wood demon- strated that amyl nitrite diminished motor energy and reflex excita- bility. Amyl nitrite is well known for its supposed efficacy as an antidote to chloroform in cases of impending death during the inhalation of the vapor of the anesthetic. A mixture of amyl nitrite and chloroform has been experimented with, in the hope of thus procuring a greater degree of safety than with chloroform alone (see Med. Bee, Oct. 5, 1878). See CMoramyl. Amylene (Beta-isoamylene; trimethylethylene ; valerene; pentene). — This highly inflammable compound was proposed as an anesthetic by John Snow in 1856; it has been used as a dental anesthetic, but great caution is necessary. See Trim ethyl e thy I e?ie and Pental. Amylene was found to produce a loss of sensibility without causing complete coma or stupor. Although Snow introduced it as a substitute for chloroform, it was found not to be so safe an agent. See Med. Times and Gaz., Apr. 4, 1857, 332; Apr. 18, 1857, 381; and Aug. 8, 1857, 133. The French Academy of Medicine formally condemned amylene as a dangerous anesthetic soon after its introduction. Eichardson {Sci. Am. Suppl., No. 515, 8227) stated that the "odor of its vapor, like wood spirit, was not pungent. Quantity of fluid re- quired for complete anesthesia, 4 to 8 fluid drachms. Eequired charge of air by vapor, 15 per cent. Anesthesia rapidly produced, with short but sharp second or spasmodic stage. Consciousness sometimes appar- ently retained during insensibility, as in somnambulism. Eecovery rapid, with freedom generally from all after-effect. Vomiting extremely rare." Eichardson stated, however, that the anesthetic value of amylene was doubtful. It caused two deaths in 238 administrations between Nov., A LIST OF ANESTHETICS 699 1856, and July, 1857. "Sudden failure of cardiac motion is the source of danger from amylene." It may be mentioned here that Mering introduced amylcne hydrate as a hypnotic in 1887. On amylene anesthesia, see also Li von : Compt. rend. Hoc. de Biol., •1903, 55, 143. Amylenechloral. — This alcoholate, formed by the combination of chloral and amylene hydrate, is Di-methyl-ethyl-carbinol-chloral, CCl3.CH.0H.0.C(CH,,),.C2H5. It is colorless and possesses a density of 1.24; its odor is camphor-like -and the taste is slightly caustic. It is insoluble in cold water, but is miscible to any desired extent with alcohol, ethyl ether, acetone, and fatty oils. Fuchs and Koch (Munch, med. WocTi., 1898, No. 37, 1175) investi- gated the properties of amylenechloral, finding it to be productive of certain sleep, deeper than that induced by chloral hydrate, when admin- istered subcutaneously or per os in dogs. It appeared to be equivalent to other hypnotics, such as paraldehyd, amylene hydrate, etc., and for this reason is included here. Amylocain. — A local anesthetic. Anemogenol. — A dental anesthetic containing novocain and supra- renin. Anemorenin. — This preparation consists of 5 c. c. of a 1 per cent solution of suprarenal extract, and another solution containing per c. c. 0.003 gm. of tropacocain hydrochlorid and 0.002 gm. of sodium chlorid. The solutions are mixed before use. Moller describes "anemorenin" as specially adapted for dental purposes. See Moller: Zahndrztl. Rmid- schau, 1902, No. 532, 9353. Anesthesin.— This local anesthetic, ethyl-para-amido-benzoate, NH,- CgH^.COOCoHs, was first prepared in 1890 by Eitsert, and was intro- duced as a substitute for cocain. It is obtained by the reduction of ethyl-para-nitro-benzoate by means of zinc and hydrochloric acid, and forms a fine white crystalline powder melting at -|- 90-91° C, and is easily pulverized. It is almost insoluble in cold water, difficultly soluble in hot water, but readily soluble in ethyl ether, alcohol, benzene, and fatty oils. It dissolves in almond oil to the extent of 2 per cent, in olive oil to 3 per cent, and those oleaginous anesthesin solutions are said to be sterilizable without decomposition. Anesthesin is decomposed into para-amido-benzoic acid and alcohol on long-continued boiling with water or on warming it with dilute solutions of the alkalies. Anesthesin was investigated from a pharmacological standpoint by Robert and Binz {Berl. klin. Woch., 1902, No. 17). Experiments on animals determined that there was no danger from the use of anesthesin in therapeutic doses. Clinical trials led to the same conclusion. In 700 ANESTHESIA physiological activity anesthesin is on a parallel with orthoform {q. v.) ; it is said to be equally effective, but free from irritant action and tox- icity. It is said to quickly render insensible to painful operations sensi- tive nerves with which it conies in contact, and to subdue pain with the same certainty as orthoform. The most delicate tissues are said to tolerate anesthesin without the slightest symptom of irritation. The anesthetic action resembles that of cocain, but is purely local; it does not penetrate the mucous membranes. In consequence of its insolu- bility, anesthesin cannot be used by hypodermic injection. See Cocainol. Some of the extensive literature on anesthesin follows: von Noorden : "On Ethyl-para-amido-benzoate as a Local Anaes- thetic," Berl Min. Woch., 1902, No. 17. Dunbar : "Contribution to Local Anaestliesia with Ethyl-para-amido- benzoate," Deut. med. WocJi., 1903, Nos. 10, 20, and 22. Lengemann : "Anesthesin in the Treatment of Wounds," Centr. f. Chir., 1902, No. 22. Kassel: "Employment of Ansesthesin," Therap. Monatsh., July, 1902, 386. Eammstedt: "On the Employment of Anesthesin Hydrochlorate (Ritsert) for Local Anesthesia," Centr. f. Cliir., 192, No. 38. Schaeffer-Struckert : "Dr. E. Eitsert's Anesthesin ; Its Employment in Dentistry," Vort. a. d. Kongr. Zahndrz. in Milnch., Aug. 5, 1902. Hartmann: "Employment of Anesthesin in Surgical Practice," Therap. der Gegenwart, Oct., 1902, No. 10. Spiess: "Anesthesin, a New Local Anesthetic, from the Point of View of the Remedial Action of Anesthesin," Miinch. med. Woch., 1902, No. 39, 1611. Geyer : "Practical Experiences with Cocainol Preparations," Reichs-Med.-Anz., Nov., 1902, No. 23. Scherer : "A Report on Four Cases Treated with Anesthesin,'"' Med. and Surg. Mon., Nov., 1902, No. 11. Glas: "Anesthesin Treatment in Laryngeal Cavities." Read in the Session of the Vienna Laryngological Society, December 3, 1902, (Ref.: Wie7ier Min. Woch., Jan., 1903, No. 1.) Earp : "A Report of Cases in Which Good Results Were Partly or Wholly Due to Anesthesin," Cincin. Lancet Clin., Dec. 13, 1902; Merck's Archives, 1903, 27. Chevalier : "Anesthesin," Rev. d. Therap., Dec, 1902, No. 24, 835. Kennel: "Anesthesin (Dr. Ritsert), A Therapeutical Trial," Bei-l. Min. Woch., Dec, 1902, No. 52, 1218. Pollatschek: "Contribution to the Treatment of Laryngeal Tuber- culosis," Magyar OriosoJt Lapja, Jan., 1903, No. 1. Henius: "Anesthesin in the Treatment of Erysipelas," Therap. d. Gegenwart, Jan., 1903 ; Merck's Archives, 1903, 99. A LIST OF ANESTHETICS 701 Maramaldi: '^Ansesthesin," Giornale inter, delle scienze-medische, Jan. 31, 1903, No. 2. Duhot : "Anaesthesin : Its Applications in Urology and Dermo- syphilography," Ann. d. I. Policlin. Central, de Brux., Feb., 1903, No. 3. Courtade : "Anaesthesin in Ehino-laryngology," Rev. d. Therap., March 1, 1903; Alle. Wiener med. Zeit., March, 1903, No. 12; Nou- veaux remedes, 1903, No. 4, 73. Duplan : "Contribution to the Study of Angesthesin," Inaugural- Dissertation, Paris, March 25, 1903. Lorand: "Contribution to the Pathology and Therapeutics of the 'Pruritus vulvae' of Diabetes," La Policlinique, Briissel, March 15, 1903. Kobert: "Ansesthesin as a Dental Anaesthetic," Pharm. Zeitung, 1903, No. 41, 413. Haug: "Anffisthesin in the Treatment of Inflammations of the Aural Passages and for Local Anaesthesia in Paracentesis," Archiv f. Ohrenheill., 1903, 58, Nos. 3 and 4, 267. Lengemann: Wiener med. Presse, 1903, 1010. Hoenigschmied : Die Heilkunde, 1904, No. 2. Imhofer: Prager med. Woch., 1904, Nos. 4 and 5. Eeinburg: Bull. gen. de therap., Feb. 23, 1904. Duhot: Ann. d. I. Policlin. Central, de Brux., 1904, No. 2. YioUet : Gaz. d. Hop., 1904, Nos. 23 and 25. Freudenthal: Med.-Pharm. Critic and Guide, 1904, No. 3. Scherer: Med. and Surg. Mon., 1904, No. 5. Lotheissen: Wiener Jclin. Rundsc, 1904, No. 44. Ivuhnt: Deut. med. Woch., 1905, No. 34. Baccarani: Soc. Med.-chir. di Modena, Seduta del 7 aprile, 1905; Baumgarten : Budapesti Orvosi Ujsdg, 1905, No. 13. Easp : Excerpta Medica, 1905, No. 5. Finder: Berl. klin. Woch., 1905, No. 8. Eeiss: Therap. d. Gegenwart, 1905, No. 10. Kassel: Z. filr OhrenheilJc., 1905, No. 1. Vohsen: Berl. Min. Woch., 1905, No. 40. Saxtorph-Stein : Hospitalstidende, 1905, No. 34 and 35 (Eef Deutsche Med.-Zeit., 1906, No. 24). Choronshitzky : Monats. f. Ohrenheil., 1905, No. 1. Klingmiiller : Deutsche med. Woch., 1905, No. 29. Lublinski: Berl. hlin. Woch., 190Q,'^o. 52. Freund: Therap. d. Gegenwart, 1906, No. 6. Eeissner: Deutsche zahndrtzl. Zeit., 1906, No. 123. Drucker: Budapesti Orvosi Ujsdg, 1907, No. 15. Avellis: Miinch. med. Woch., 1907, No. 11. Bruhn: Therap. Neuheiten, 1908, No. 2. Hoffman: Miinch. med. Woch., 1908, No. 14. 702 ANESTHESIA Payr: Med. Klinik, 190S, 'No. 18. Frese: Med. Klinik, 1908, No. 16. Karabinski: Aerztlicher Central-Anzeiger, 1909, No. 17. Eitter-Bier: Vortrag auf der 38. Verhandlungen der deutschen Gesellschaft .fiir Chirurgie, 13-17 April, 1909. Allg. med. Central- Ztg., 1909, No. 21. Pinner and Siegert: Berl. hlin. Wocfi., 1909, No. 22. Fackelmann: Allg. med. Central-Ztg., 1911, No. 3, 32. Anaesthesin Solubile (Dr. Ritsert). — According to Pharm.-Ztg., If!, 460, this is a form of Ritsert's anesthesin marketed by a Frankfort firm. Anaesthesin Bomelin. — Bormelin containing 10 per cent anesthesin. Anaesthesinum Solubile. — See Suhcutin. Anaesthesinum Sulfophenylicum. — See Suhcutin. Anesthol. — A liquid of red color, ethereal odor, and bitter taste, used as a local anesthetic in dental practice in Germany. Anesthetic Mixture (Reynes). — This consists of chloroform, 2 parts; ether and absolute alcohol, 1 part each. Coblentz : "The Newer Reme- dies," 4th ed., 12; Gehe's Codex, Nov., 1910, 21. Anaesthetica Tabletten. — A German dental anesthetic for injection into the gums, containing atropin sulphate, 0.0003 gm. ; morphin hydro- chlorid, 0.005 gm. ; cocain hydrochlorid, 0.01 gm. ; potassium ortho-oxy- chinolin-sulphonate, 0.0007 gm. ; and sodium chlorid, 0.014 gm. One to two tablets are dissolved in 2 to 4 c. c. of water. Anaestheticum. — A dental anesthetic, said to be a 10 per cent solu- tion of cocain in phenyl acetate. Anaestheticum (Edison's). — This contains chloral, 30 parts; alcohol, 110 parts; chloroform, 90 parts; camphor, 60 parts; oil of cloves, 59 parts ; oil of peppermint, 59 parts ; ethyl ether, 50 parts ; salicylic acid, 5 parts; amyl nitrite, 3 parts; and morphin sulphate, 2 parts (Coblentz: "The Newer Remedies," 4th ed., 12). Anaestheticum Bottwini. — A mixture of 3 parts by weight each of menthol and crystalline phenol, with 1 part of cocain hydrochlorid. Anaestheticum Gray. — See Gray's AncBstheticum. Anaestheticum Witte. — A dental local anesthetic, consisting of a so- lution of methylbenzoylecgonin hydrochlorid and hydroiodid in solution in sterilized physiological salt solution containing iodin and phenol. Anaesthin and Anaesthol (Speier). — A mixture of five parts of ethyl chlorid and 1 part of methyl chlorid. Employed as a local anesthetic by spraying. See Z. angew. Chem., 1901, 261. Anaesthol Katz. — A local anesthetic containing methyl chlorid and ethyl chlorid. Anaesthol (W. Meyer); Weidig's Anaesthol; Anesthol. — Schleich ("Schmerzlose Operationen," II Aufi., Berlin, 1897) endeavored to im- prove general anesthesia by starting from a physical instead of from a A LIST OF ANESTHETICS 703 chemical basis. Without ignoring any of the important points in ad- ministration, he attempted to adapt the boiling point of the narcotic to the temperature of the body. As is well known, chloroform possesses a boiling point considerably above the body temperature, while ethyl ether boils somewhat below the same. In consequence thereof, Sohleich reasoned that chloroform, when administered by inhalation for the pro- duction of narcosis, is absorbed by the blood in larger amount than is really necessary for the purpose. Furthermore, since it is eliminated by the organism gradually, it overtaxes all the parenchymatous organs, in- juring, as a result thereof, their cells. On the other hand, ether is va- porized so rapidly Avhen inhaled that it will not enter the blood if the alveoli do not first become overfilled with carbon dioxid, producing pri- mary cyanosis and dyspnea. To quote Willy Meyer {Med. Rec, Aug. 15, 1908) : "It is with the onset of this cyanotic condition, it seems, that the narcotic effect of the ether begins. Although the elimination of ether almost keeps pace with its absorption, the slight excess that remains in the blood is sufficient to affect the brain and produce uncon- sciousness. The greatly accelerated rhythm of breathing, which in- creases the amount of oxygen inhaled, facilitates the elimination of carbon dioxid by the laws of diffusion of gases involved in normal res- piration." It follows from this reasoning that the essential condition for the regular elimination of ether in a state of vapor is an absolutely intact lung — one able, if required, to perform an abnormal amount of work. In view of the preceding, Schleich sought a safer narcotic which would not tax the parenchymatous organs or the lung tissue, and one possessing a boiling point corresponding to the body temperature, in order that the amount eliminated during expiration should be about equal to that absorbed during inspiration. He finally selected a com- bination of chloroform, ether, and petroleum ether (benzin), the latter being added for the purpose of diminishing the toxic effects of chloro- form upon the system. Schleich employed three mixtures (see Schleich: "Ansesthetics"). Notwithstanding the position taken by Dawbarn {Atlanta Med. Surg. J., Sept. and Oct., 1897) and others, it is a fact that in practice mixtures have proved to be safer than ether or chloroform alone (on this point see Meyer: J. Am. Med. Assn., Feb. 28, 1903). English anesthetists have, for instance, experienced great success with A. C. E. mixture {q. v.), and it has also been reported from Vienna that Vienna mixture {q. v.) possesses great safety. Schleich maintained that such anesthetic mixtures were chemical solutions, not mixtures, possessing a boiling point differing from that of any of the components. Ellis ("Ana3sthesia with Mixed Vapors," London, 1866) had earlier found that, when London Medical and Chirurgical Mixture A. (alcohol, 1 part; 704 ANESTHESIA chloroform, 2 parts; and ether, 3 parts) was evaporated, during the six or seven minutes required for the evaporation of tvi^o grams of the liquid, the vapor of ether, almost exclusively, was given off during the first minute, the vapor of chloroform predominated during the next three minutes, and the evaporation of alcohol occupied the last three minutes. H. P. Weidig, of Newark, JSF. J., found, on analyzing Schleich's an- esthetic mixtures, that "they contain a permanent nucleus — a chemical combination of chloroform and ether, according to their molecular weight" (Meyer: J. Am. Med. Assn., Feb. 28, 1903). Meyer reports that 43.25 parts of pure chloroform by volume and 56.75 parts of abso- lute ether by volume, mixed together, "enter into chemical combina- tion" (see "M. S."), forming "a stable molecular solution," which re- sists fractionation to the last, and which has an evaporating point of its own. According to Weidig (see Meyer, Loc. cit.), Schleich's mixtures contain "this fixed molecular solution of chloroform and ether ("M. S.") plus 36 to 53 per cent (in volume) of free ether, plus petrolic ether, the latter most probably not in chemical combination." Meyer there- fore concluded that patients subjected to general anesthesia by means of Schleich's mixtures inhale in the beginning of the narcosis ether plus "M. S." plus petrolic ether. After the ether and petrolic ether have evaporated the narcosis continues with "M. S." Meyer considered Schleich's principle of improving general anesthesia on a physical basis to be correct, but was obliged to abandon the use of his mixture, in view of the findings of Meltzer (N. Y. Med. Bee, 1898, 607; Aug. 15, 1908), whose experiments showed that petrolic ether had no narcotizing power and produced paralysis of the respiratory muscles if administered in large amount. After numerous experiments during 1897 and 1898, Weidig and Meyer tried ethyl chlorid as a substitute for petrolic ether, and found that a mixture of 18 per cent by volume of ethyl chlorid plus 82 per cent by volume of "M. S." possessed a boiling point of -|- 100.4° F. (-j- 38° C), that 17 per cent by volume of ethyl chlorid plus 83 per cent by volume of "M. S." had a boiling point of + 104° F. (+ 40° C), and that 16 per cent by volume plus 84 per cent of "M. S." had a boiling point of + 107.6° F. (+ 42° C). Meyer proposed that only the second mixture be used, namely, that containing 83 per cent by volume of "M. S." plus 17 per cent by volume of ethyl chlorid, and he used this new mixture, which was termed "anesthol" or "ansesthol," for the first time on October 15, 1898, in an interval operation for appendicitis. Meyer has stated {Med. Bee, Aug. 15, 1908) that the combination was trade-marked "anesthol" by the manufacturers much against his will, but it is not patented, and has been marketed also under the name "ansesthol." A LIST OF ANESTHETICS 705 Anesthol is a clear, transparent liquid of very agreeable odor, pos- sessing a density of 1.045 and a boiling point of -f 1<^4° F. (-f- 40° C). "It is," to quote Meyer, "a chemical combination of ethyl chlorid and M. S., not a mixture; for, on evaporating 1,000 c. c. of anesthol for five hours at a uniform temperature of + 104° F., 22 c. c. (2.2 per cent by volume), with a specific gravity of 1.262, were left. . . . This fact proves that up to the last moment a 'solution of components' dis- charges, and does not leave a final residual chloroform, . . . as is the case in Schleich's mixtures (Weidig)." Weidig found, upon analy- sis, that anesthol contains 17 per cent of ethyl chlorid, 35,89 per cent of chloroform, and 47.10 per cent of ether (method of analysis not stated in Meyer's communications). "Gelie's Codex" (Nov., 1910, 22) gives the composition of "ansesthol Meyer" as: 17 per cent ethyl chlo- rid, 31,7 per cent ether, and 51.5 per cent chloroform. In the same place "anesthol" is described as a mixture of chloroform, 43.25; ether, 56.75; and ethyl chlorid, 20.5. Schleich later adopted the combination recommended by Meyer, substituting ethyl chlorid for petrolic ether; he again proposed three different mixtures, which, to quote Meyer, "is not practical." Meyer {Med. Bee, Aug. 15, 1908) stated that he had used anesthol in his hospital and private work for ten years, and that it was also ex- tensively employed by his colleagues at the German Hospital, New York. Early in the fall of 1899 they introduced the rule of giving a hypo- dermic of morphin about one hour prior to the administration of the general anesthetic, "We have used the chloroform, ether, and ethyl chlorid mixture in many thousands of cases, . . . and consider it, when preceded by a hypodermic of morphin, the least dangerous of all anesthetics thus far known, especially in the hands of comparatively in- experienced anesthetists, and this not only as regards the safety of the patient while on the operating table, but principally as to the after- effects of the anesthetic (Meyer)," On anesthol, see the following papers: Meyer: J. Am. Med. Assn., Feb. 28, 1903; Meyer: Munch, med. Woch., 1903, 1221; Katz: Deut. med. Woch., 1903, 431; Forster: Centr. f. Gyndkol., 1903, No. 24; Klin.-iherap. Wocli., 1903, No. 32; Heger: Pliarm. Post, 42, 373; see also, Pharm. Ztg., ^8, 544; Meyer: Med. Bee, Aug. 15, 1908. Eosenthaler {Archiv der Pharmazie, Berlin, 1906, 244, 24) found that chloroform and ethyl ether, both at -|- 15.2° C, mixed in the proportion of their molecular weights, increased in temperature to -f 30.2° C, Mme. and H. Marcelet (Bull. Sci. Pharmacol., Nov,, 1912, 676) also referred to the disengagement of heat observed on mixing chloroform and ether, and they investigated the effects on mix- ing the two liquids in varying proportions, using chloroform which had been carefully freed from alcohol. With a mixture of 25 c. c. of each ro6 ANESTHESIA liquid, the temperature rose from an initial of + 1G.55° to -|- 30.3° C. Whether the evolution of heat noted upon mixing ether and chloro- form is due to solution or reaction, the above mentioned authors did not attempt to explain. With the view of throwing some light upon this question, in §o far as it pertained to the contention of Weidig (loc. cit.) that 43.25 parts of chloroform and 56.75 parts of absolute ether by vol- ume, mixed together, "enter into chemical eombination," Baskerville,^ assisted by N^eidle, made an experi- mental investigation of the rise of temperature when chloroform and ethyl ether are mixed. The ethyl ether used in. the ex- periments performed by Baskerville and Neidle was "anhydrous ether"; but it contained about 0.1 per cent water and 0.8 per cent ethyl alcohol. Such a grade was used because an ether containing minimum quanti- ties of water and alcohol was de- sired. The chloroform used was "chloroform, U. S. P.^^ (anesthetic chloroform) ; it contained approxi- mately 1 per cent of 95 per cent ethyl alcohol. In the first experiments both the chloroform and ether were taken at -f- 15.3° C, in order to repeat the work of Rosenthaler. The apparatus is shown in Figure 280. As the working temperature was below the room temperature which obtained, this was maintained by adding ice to the water bath. On account of the greater volatility of the ether, in most of the experiments the chloroform was run out from the constant temperature bath first, and then the ether was added to the vessel containing the measured amount of chloroform. A small conical vessel with rather a narrow neck was used for mixing. Results. — From the results presented in Table I (see p. 707) it will be seen that the maximum rise in temperature is obtained in the case of the molecular mixture. The investigation of Philip (Z. jjhysikal. Chem., 1897, ^^, 18) on the dielectric properties of this molecular mixture indicated that it might be an individual chemical compound. However, Baskerville and Keidle found that, on boiling, it behaved like a mixture, and not like a compound; that is, it begins boiling, when fractionated, near the ^ Charles Baskerville : ' * An Investigation of ' M. S. ' " Fig. 280. — Apparatus Used by Basker- ville AND Neidle. a, an inverted bell-jar; B, a rubber-stopper support- ing the bath of water and containing two burettes, one for ether and the other for chloroform; C, an arrange- ment for agitating the bath by means of compressed air; D, a thermometer. A LIST OF ANESTHETICS TABLE I 707 Per Cent of Chloroform Temperature of mixture in 1. By volume 2. By weight 3. Molecular degrees C. 11.1 20.4 13.9 23.7 20.0 34.1 24.4 26.9 33.3 50.9 39.2 30.6 42.8 60.9 49.1 32.5 50.0 67.5 56.3 32.4 55.6 72.2 61.7 31.9 60.0 75.6 65.9 31.4 63.6 78.4 69.3 31.0 66.6 80.6 72.1 30.1 69.2 82.3 74.4 29.5 72.7 84.7 77.5 29.0 80.0 89.2 83.7 26.9 88.9 94.3 91.2 23.7 = 0500 boiling point of ethyl ether, and gradually rises to the boiling point of chloroform. This indicated that the heat developed when ethyl ether and chloroform are mixed was largely, if not entirely, heat of solution, and that the molecular mixture gave the greatest increase in tempera- ture was accidental. This conclusion, based upon the observations re- corded above, is hardly supported by the work of Baskerville and Singer, which indi- cates that there is a compound of EtgO and CHCI3 existing in equilibrium with the components of the solution (see Basker- ville and Singer, in- fra). In Table II are given the calculated heats given out by 100 gm. of the various mix- tures, on the assump- tion that the specific heats are additive. This assumption is justified by the small coefficient of contraction even in the case of maximum con- traction. If the heat generated by mixing ether and chloroform were mainly attributable to the formation of a molecular compound, the heat in mixture 4 should be nearly three times that in mixture 1, for three 20 30 40 50 60 70 Molecular Per cent Chloroform 80 90 Fig. 281. -Graph Showing the Heat Generated by Mixing Ether and Chloroform. 708 ANESTHESIA times as much of the compound could be formed. In the graph repre- senting these quantities of heat (Fig. 381), a break is observed at the molecular mixture, which may be explained by the large difference be- tween the specific heats of ether and cliloroform. In Table III are the calculated quantities of heat produced on add- ing successively increasing quantities of chloroform to 100 gm. of ether. Georgiewsky {J. Russ. Pliys.-Chem,. Soc, 1902, SJf., ii, 565) gives the coefficient of contraction between ether and chloroform as 1.4 per cent at temperatures between 4-20° and -f- 22° C. Baskerville and N'eidle found the coefficient of contraction at -|- 30° C. to be 1.5 per cent. 30° Ether — d — = 0.70305 4° 30° Chloroform — d — = 1 . 4658 4° 30° Molecular mixture — d — = 1 .0514 4° TABLE II Molecular per cent Calories given out by chloroform 100 gm. of mixture 1 13.9 392 2 24.4 494 3 39.2 577 4 49.1 598 5 56.3 552 6 61.7 523 7 65.9 492 8 69.3 72.1 467 9 432 10 74.4 407 11 77.5 383 12 83.7 310 13 91.2 213 TABLE III Grams of CHCI3 added to 100 gm. of ether Heat generated in calories 1 25.6 51.7 103.7 155.8 208.6 259.7 309.8 363.0 415.5 492 2 750 3 1175 4 1529 5 1704 6. 7 8 1881 2016 2162 9 2227 A LIST OF ANESTHETICS 709 In the experiments performed by Baskerville and Singer "M. S." was investigated along different lines from those described above, in or- der to ascertain whether ether and chloroform, mixed in the proportions stated by Meyer {loc. cit.), form a "stable molecular solution." Density of residual solution at + 23.5° C. After the evaporation of 50 c.c 1 . 0788 100 " 1.1010 150 " 1.1134 200 " 1 . 1325 250 " 1 . 1469 300 " 1 . 1640 350 " 1 . 1866 The ethyl ether used possessed a density of 0.7113 at -)- 23.5° C; the chloroform, a density of 1.4786 at -(- 23.5° C. ; and the "molecular solution," a specific gravity of 1.0G45 at -|-23.5° C. In the preparation of the "molecular solution," upon mixing the ether and chloroform, con- siderable heat was developed, as noted by Baskerville and Neidle. Five hundred c. c. of this solution were placed in a gas absorption bottle, and a regular current of compressed air, previously purified, was passed through, the current being about the same as that used in the Gwathmey method of vapor an- esthesia. The vapors were conducted through a glass worm condenser and a train of Wolff bottles, sur- rounded by ice, but very little of the evap- orated solution could be condensed. The density of the residual solution was then determined after the evaporation, at room tempera- ture, by means of the aforesaid air current, of each 50 c. c. The results obtained from duplicate experiments were as given in the table above. The remaining 150 c. c. were then removed from the gas absorp- tion bottle, and evaporated down to 25 c. c. This residue possessed a density of 1.3075 at + 23.5° C. It will be seen from these results that the components of the solu- tion do not come off in order under the described conditions: but the 1.2000 1.1900 1.1800 1.1700 1.1500 1.1500 1.1400 1.1300 1.1200 1.1100 1.1000 1.0900 1.0600 1.0500 <5 / / / / y / / / / / / / / / / / / ' / y t / / / / A / / / / y / ''A / y /o 50 100 150 200 250 300 350 AB = Ether-Chloroform Line CD = Anesthol Line Fig. 282. — Graph Showing Densities of Residues. 710 ANESTHESIA chloroform and ether are evaporated together, although the ether comes off ill much greater quantity. The solution itself, of course, is not a chemical compound, but the results indicate that a compound of chloro- form and ether exists. As Meyer observed, a "solution of components" is evaporated) and residual chloroform does not remain. In Figure 282 the results obtained on "M. S." are shown by line AB. Similar experiments were performed with "Dr. Weidig's Anaesthol," claimed to be a stable "chemical union" of 35.89 per cent chloroform, 17 per cent ethyl chlorid, and 47.10 per cent ethyl ether. The anesthol possessed a density of 1.0538 at -\- 23.5° C. Using 400 c. c, and oper- ating as in the case of "M. S.," the following results were obtained : Density of residual solution at + 23.5° C. After the evaporation of 50 c .c 1 . 0815 " " " "100" 1.1076 " " " " 150" 1.1344 " " " "200" 1.1625 " " " "250" 1.1913 The last 25 c. c. possessed a density of 1.2590 In Figure 282 the results obtained on anesthol are shown by line CD. In the case of anesthol the lines of distillate and residue are both straight and nearly parallel. Undoubtedly anesthol contains a compound of chloroform and ether in equilibrium with the components of the solution. Ansesthyl (Anestyle). — A mixture of 1 part methyl chlorid and 5 ,parts ethyl chlorid, for the production of anesthesia by freezing in ;deiital operations. i Ansesthyle. — See Ancesthol (W.Meyer). Ansestiform (Oppenheimer). — Cocain hydrochlorid and renaglandin in distilled extract of witch hazel, containing, in addition, the sul- phates of sodium and ammonium (Coblentz: "The Newer Eemedies," 4th ed., 12). According to Heger (Pharm. Post., J^2, 373), anasstiform is a solution of renaglandin, cocain hydrochlorid, and sodium sulphate in albumin. Anaezol. — An antiseptic local anesthetic containing, in solution, thymol, menthol, alcohol, benzoic acid, carbolic acid, oils of wintergreen and eucalyptus, glycerin, boric acid, indigo, and 1 per cent cocain. Analgos (Stephan). — A dental local anesthetic consisting of a mix- ture of thymol, menthol, phenol, aspirin, and sodium chlorid, each 1 gm. with 0.5 of cocain hydrochlorid, dissolved in 95 gm. of diluted alcohol. Andolin. — A cocain-free local anesthetic. See Mayer, Monatsh. f. prakt. Dermatol., 1907, J^5, 603. It is said to consist of 0.5 gm. eucain B, 0.75 gm. stovain, 0.008 gm. suprarenin hydrochlorid and physiological A LIST OF ANESTHETICS 711 salt solution to make 100 gm. Andolin is marketed by a I'>erlin eoiiceni, being sold in sealed tubes containing 2 e. c. for dental practice. See Pharm. Ztg., 53, 161. Anesin or Aneson. — An aqueous solution of 1 per cent 9,eetone- chloroform (see Chloretone and Methaform) ; a local anesthetic, and also substitute for cocain in infiltration anesthesia and in Oberst's regionary anesthesia. On the chemistry of Anesin, see Cohn : Pharm. Zentralhalle, JfO, 33 ; and Vamossy: Apoth.-Ztg., 12, 608. On the application of Aneson, see the following contributions : Vamossy: Ungar. med. Presse, 1897, No. 21; Deut. med. Woch., 1897, No. 36. Sternberg: Klin.-therapeut. Wocli., 1898, No. 39, 1398. Eubinstein : Med.-Ztg., 1898, No. 33. Hanzel: Wien. Min. Woch., 1898, 1123. Mosbacher: Munch, med. Woch., 1899, No. 3, 81. Impens : Arch, intern, de Pharmacodymie, 1901, 8, 77. Anesthaine. — This is a local anesthetic, "each fluid ounce of which contains 5 gm. of stovain with synergistic antiseptics in a sterile and ready-to-use solution." Anesthia. — See Ancesthesin. Anesthesin Sulphophenate, or Sulphophenalylate or Sulphocarbo- late. — See Subcutin. Anesthol (Meyer). — See Ancesthol (W. Meyer). Anesthol (Weidig). — See Ancesthol (W.Meyer). Anesthone-Creme. — Adrenalin hydrochlorid, 1 : 20,000 ; paramido- ethyl benzoate, 10 per cent, with a salve (bland oleaginous) base. Anesthone-tape. — Gauze which has been treated with a solution of adrenalin hydrochlorid (1:20,000) and 5 per cent of paramido-ethyl benzoate. Anestile (Ariesthyl). — A local anesthetic containing methyl chlorid, 1 part, and ethyl chlorid, 5 parts. This preparation, formerly known as an'estyle-bengue, is a mixture of ethyl and methyl chlorids. See Z. angew. Chem., 1901, 261. Anestol. — This is an anesthetic balm intended for local application in neuralgia, headache, etc. It is said to consist essentially of menthol and methylsalicylate in a readily penetrating ointment base. Anestyle. — See Ancesthol. Anestyle-bengue.^See Anestile. Anodyne. — See Ethyl Chlorid. Anodynone.— -This is a trade name for Ethyl Chlorid (q. v.). Antemesin. — This is a fanciful designation for capsules containing 1-1.2 grs. of anesthesin {q. v.) ; it is used as an anodyne in gastric ul- cer, dyspepsia, etc. 712 ANESTHESIA Antidolorin. — A "purified" ethyl chlorid, used as a local as well as an inhalation anesthetic. Antipyrin (Dimethyloxyquinizin) . — To quote Heineck ("General and Local Anesthesia," 1900, 79) : "Antipyrin is valuable to obtain an- esthesia of the urinary bladder. Its anesthetic power is less than that of cocain, but it has the advantage of being less toxic." Using as a test object one of the lower legs of a frog immersed in 5 c. c. of the solution to be tested, and determining the concentration necessary to produce complete numbness in 30 minutes, Bela von Isse- kutz (Arch. ges. Physiol., lJf5, 448) found that 2.5 per cent cocain, 3,2 per cent eucain-B, 6 per cent novocain, and 5 per cent antipyrin pro- duced numbness. Employed together, antipyrin increased the action of cocain 46 per cent, of eucain-B 39 per cent, and of novocain 19 per cent. The employment of antipyrin as a local anesthetic has been dis- cussed in the following reports: Brick: "De Faction calmante de I'antipyrin chez les prostatiques," Semaine med., 1894, 128. Heinze: "Experimentelle Untersuchungen liber Infiltrationsanas- thesie," Virchows Archiv, 1898, 153. Kocher: (Antipyrin-cocain solutions) "Operationslehre," 4th ed., 202. Lydston: "Antipyrin as a Local Anesthetic," J. of Cutaneous and Genito-urinary Diseases, May, 1898. Pousson: "Analgesic vesicale par I'antipyrin," J. de Med. de Bor- deaux, May 19, 1895. Vigneron: "Analgesic vesicale par I'antipyrin," Ann. des Maladies des Org. genito-urin., 1894, 348. Antivom. — Anesthesin tablets, used in nervous dyspepsia, seasick- ness, etc., and in chloroform narcosis. Apinol (Apinolum). — Apinol is a product obtained in the destruc- tive distillation of the wood of pinus palustris and pinus australis. It is claimed to consist mainly of Isevomenthon, C^JIj^gO. Apinol is obtained from the products of destructive distillation of pine wood. After the removal of turpentine and other low boiling con- stituents by distillation, the portion boiling between + 182.2°-193.3° C. (360°-380° F.) is collected and purified. It is a clear amber-colored oil with an odor resembling that of the pine, having a specific gravity of 0.946 and an approximate boiling point of + 182.2° C. (360° F.). It is neutral in reaction. Actions and Uses. — Apinol is said to be an antiseptic, local anes- thetic, and expectorant. It is said to be useful when applied externally to wounds, burns, ul- A LIST OF ANESTHETICS 713 cers, and denuded surfaces for the relief of pain and promotion of healing. Apotheker Maier's Radikal-Anasthetikum. — See Eadikal-A'nllslheii- Tcum. Arabic Acid Salts with Anesthetic Bases. — Erhardt, in German Patent of May 32, 1908, No. 211,800, claims a process for manufacturing salts of arable acid with anesthetic bases, consisting in acting with pure arable acid on cocain, tropacocain, stovain, novocain, and analogous compounds. Erhardt {Arch. Intern. Pharmacodyn., 21, 237) stated that the arabinates of cocain produced fewer toxic symptoms than the chlorids. The arabinate anesthesia lasts two to four times longer than that due to chlorids; the mucilaginous elements of the arabinates render the anesthetizing bases less irritant, and, according to Erhardt, a higher grade of anesthesia can be produced than with the chlorids. Aran's Anaesthetic Ether. — See /Ether Ancestheticus Aranii. Arnold's Dental Anodyne or Local Anaesthetic. — Acetic acid is neu- tralized with ammonium carbonate, and the mixture is saturated with salicylic acid. The wJiole is then filtered and treated with cocain hy- drochlorid (Eng. Pat., 1887, No. 7061). Barker's Anesthetic. — Arthur E. Barker, of London, recommended the following formula for the anesthetic solution in infiltration anes- thesia : Eucain, 1 part by weight; sodium chlorid;, 8 parts by weight; water, 1,000 parts by weight. Heineck's "General and Local Angesthetics," 1900, 115. Benesol. — A local anesthetic used in dental surgery and containing eucain-B, cocain hydrochlorid, phenol, menthol, eucalyptol, and amyl nitrite, in solution in sterilized distilled water. On this local dental anesthetic, see Heger: Pliarm. Post, Jf-3, 373. Bengue's Mentholdragees. — These are said to contain menthol and sodium borate, with 0.001 gm. cocain. Benzcain. — Guaiacol benzoate, or benzyl ester ; a local anesthetic. Benzene (Benzol). — John Snow, in 1818, found that benzene is an indifferent anesthetic with severe after-effects. Simpson (1818) found that benzol is capable of producing anesthesia by inhalation, but "ring- ing and noises in the head are excessive." It was also tried by T. JSTun- neley in 1849. The inhalation of benzol vapor was found to produce narcotic ef- fects, but with some symptoms indicative of a noxious action on the brain and spinal cord (Stone: Med. Gaz., 1848, J/.!, 1077). It may be mentioned that liquid benzol is said to act as a narcotic ("Anilin und Anilinfarben/' 1864, 13). Eichardson (Sci. Am. SuppL, No. 515, 714 ANESTHESIA Nov. 14, 1885, 8227) reported that benzol vapor is heavy and disagree- able to breathe; that the action is determinate, but slow; and that the anesthetic value is very indifferent, and the after-effects severe and prolonged. Benzene is said to produce slight paresis of the voluntary muscles, but its principal action is on the higher cerebral centers, pro- ducing lethargy and somnolence. Later a kind of "intention tremor" occurs in the voluntary muscles. Naphthalene is less toxic than benzene, and pyrrol, furfurane, and thiophene resemble benzene to a certain ex- tent in their physiological action. On the influence of benzene on the organism, see Arch. Hygiene, 1911, 75, 1-119. "Benzine" is less toxic than benzene. See Carbon Tetraclilorid. Benzenoform. — See Carbon Tetrachlorid. Benzineroid. — See Carbon Tetrachlorid. Benzinoform. — See Carbon Tetrachlorid. Benzoylamincethanol. — The hydrochlorid forms long, slightly solu- ble needles, melting at + 125° C. It possesses anesthetic properties. Benzoyl-beta-hydroxy-tetrametliyl-pyrrolidiii. CH, CH, C CHj NH CHs C CH.Q.COCeHj CHj, This has, it is said, a powerful local anesthetic action; it is also said to be less toxic than beta-eucain (Francis and Fortescue-Brickdale : "The Chemical Basis of Pharmacology," 1908, 309). Benzoyl-ethyl-dimethylaminopropanol-hydrochlorid. — See Stovain. Benzol Peroxid. — This compound, CgHg — CO.O2.CO — CgHg, con- sists of white crystals fusing at -|- 103.5° C, and freely soluble in alco- hol, ether and carbon disulphid, more sparingly in water and fatty oils. It is odorless and keeps well. Loewenhart (Therap. Monatsh., 1905, No. 8, 426; Bull, de Pharm du Sud-Est, 1905, No. 10, 569) recommended benzoyl peroxid as a use- ful antiseptic. From his observations, when applied locally as a powder and in the form of a solution, it does not produce symptoms of irrita- tion, but causes a mild anesthetic effect. Benzoylpsendotropein. — See Tropacocain. Benzoyl-triacetone-alkamin-carboxyl. A local anesthetic, which has not, to our knowledge, been marketed. A LIST OF ANESTHETICS 715 CH, Clia C CH2 I I /O.COCbHs NH C< I I ^COOH CHs C CH2 I CH« Benzoyl-tropein. — A local anesthetic. It is described as a soluble compound in silky needles. Filehne {Berl. hlin. Woch., 1887, 7) found that benzoyl-tropein is a powerful local anesthetic. He also reported that other benzoyl com- pounds are local anesthetics. According to Filehne, benzoyl methyl tri- acetonalkamin is the most powerful, benzoyl quinin is next, and benzoyl morphin is the least. Benzoyl Vinyl Diacetonalkamin. — See Eucain-B. Benzyl-morphin. — See Peronin. Beta-benzoyloxy-l)eta-3:4-niethylenedioxyphenyletliyldiniethylaniin. — This compound is an example of local anesthetic alkamin ester de- rived from secondary alcohols and containing only two carbon atoms between the acyl and amino groups. It is built on an adrenin skeleton, and is said by Jowett and Pyman (Proc. of 7th Internat. Cong, of Ap- plied Chem., Section IVa, 1) to have very considerable local anesthetic action. Betacain. — See Eucain-B. Beta-ethyletramethyldiaminoglycerin Benzoyl Monochlorid. — Said to be of value as a local anesthetic. Beta-eucain. — See Eucain-B. Beta-gamma-dibenaoyloxy-dimethyl-propylamin. — This compound is an example of local anesthetic alkamin ester derived from secondary alcohols and containing only two carbon atoms between the acyl and amino groups. See Jowett and Pyman: Proc. of the 7th Internat. Cong, of Appl. Chem., Section IVa, 1. BilLroth's Mixture A. C. E. — Alcohol, 1 part; chloroform, 3 parts; and ether, 1 part. Mix. See Hewitt: "Angesthetics and Their Adminis- tration," 3rd ed., 467. According to Buxton (p. 292), Billroth's mixture may be considered an alcohol-chloroform mixture of 20 per cent alcohol. It is said by the same authority to have no advantage over the "1 in 10 mixture." Ter- rier and Peraire ("Petit manuel d'anesthesie chirurgical," 1894, 179-80) give the following formula: Chloroform, 100 gm. ; alcohol, 30 gm. ; and ether, 30 gm. "This anesthetic mixture is used in the surgical clinics at Vienna by Billroth, Albert, Mosetig, Moorhof, etc." The 716 ANESTHESIA formula given by Terrier and Peraire was communicated to Lermoyez, who assisted at many practical anesthesias in Vienna, by Eiselberh, the assistant to Billroth. Blue Light. — E. C. Titus has reported that blue light possesses anes- thetic properties. In his experiments he employed a series of glass rods about 1/8 inch in diameter, placed side by side and tied together to form a flexible mat. The glass used was cobalt blue, so that no red rays would be transmitted. When the glass-rod mat was placed upon the part to be anesthetized, and a tungsten lamp was brought thereover as closely as possible, in about twenty minutes the part became insensitive, so that superficial and even deep incisions were not felt. Bonain or Bonainsche Mixture. — This consists of equal parts of crystalline menthol, cocain hydrochlorid, and pure carbolic acid, with or without 1 per cent adrenalin. Boro-chloretone. — A mixture of boric acid, 3 parts, and chloretone, 1 part, used as an antiseptic anesthetic, especially as a dusting powder in painful wounds. Borsain. — This anesthetic, according to Rabow (Chem.-Ztg., 1912, ISTo. 23, 206), consists of pure carbolic acid, menthol, and cocain hydro- chlorid, aa. On its use, see Mource: La clinique, 1911, No. 6. Brandwundenol. — A colorless and odorless oil with an addition of co- cain or eucain. Braun's Solutions for Anesthesia. — I. Cocain hydrochlorid, 0.1; physiological salt solution, 100.0; 1 per cent suprarenin solution, 5 drops. II. Cocain hydrochlorid, 0.1; physiological salt solution, 50.0; 1 per cent suprarenin solution, 5 drops. III. Cocain hydrochlorid, 0.05 ; physiological salt solution, 10.0; 1 per cent suprarenin solution, 10 drops. IV. Cocain hydrochlorid, 0.05; physiological salt solution, 5.0; 1 per cent suprarenin solution, 10 drops. Braun's Suprarenin Tablets. — These contain 0.00013 gm. suprarenin borate, 0.01 gm. cocain hydrochlorid, and 0.009 gm. sodium chlorid. They are used for the production of local anesthesia, particularly in dental surgery. Brenzcain. — Pyrocatechin-methyl-benzyl ester, or guaiacolbenzyl es- ter, r TT /OCH3 ^^•XOCHo.CeHs, forms colorless crystals, soluble in alcohol, ether, and vasogen, and fus- ing at 4- 62° C. The irritant action of guaiacol on the mucous membranes suggested the desirability of the existence of a preparation which might possess all the advantagepus properties of guaiacol without its disadvantages. Brenzcain seemed to satisfy this requirement, and was accordingly used by Marcus for the induction of local anesthesia by means of cata- A LIST OF ANESTHETICS 717 phoresis (Dent. nied. Woch., 1897, ISTo. 10; Bericht ilber die Verhand- lung des C entral-V ereins Deutscher Zaimdrzte, 1897, 409). See Cocain Tlydriodid. Brenz (Pyro) Catechin Methyl -benzyl Ether. — See Brenzcain. Bromal. — Tribromacetaldehyd hydratetl, CBr3.GH(0H)2, causes ir- ritation of the respiratory passages in animals ; larger doses produce dysp- nea and cyanosis; still larger doses cause anesthesia, but not hypnosis. On the anesthetic properties of Bromal, see Steinauer: Virchow's Archiv f. path. Anat. u. Phys., May 19, 1870. Bromic Ether. — See Ethyl Bromid. Bromoform (Tri-bromo-methane; Formyl tribromid). — When pure this compound is a colorless liquid solidifying at -|- 8° C. and boiling with slight decomposition under ordinary pressure at -|- 151° C. It possesses a specific gravity of 2.902 at -j- 15° C, but with 1 per cent of ethyl alcohol present the density is 2.885 at -)- 15° C. The ordinary preparation deteriorates rapidly. Bromoform of the Deutsches Arzneihuch V. contains 4 per cent alco- hol, and has the density 2.829-2.833. It boils at + 148-150° C, and has a solidification point of -|- 5-6° C. Feist and Garner (Arch. Pharm., 21^9, 458) made experiments with bromoform carefully purified, and bromoform to which was added 4 per cent ethyl alcohol ; they found the density to be 2.6354, the boiling point to be -|- 146.25° C, and the solidification point to be -)- 4° C. As early as 1849 ISTunneley and Schuchard proposed bromoform as a general anesthetic. The later experiences of anesthetists have shown, however, that, although bromoform produces a rapid narcosis when in- haled, its use is attended with great danger. On bromoform poisoning, consult Gerson: Aerztl. 8achverst.-Ztg., 1910; Zentr. f. d. ges. Therap., 1910, 447. Brucin. — Brucin in 5 per cent solution was, at one time, employed as a local anesthetic, but it was abandoned because it did not give uniform results; it was not readily absorbed, and had none of the advantages of cocain. See Heineck : "General and Local Anesthetics," 1900, 78. On the physiological action of brucin, see Mays: Therap. Gaz., June, 1885. On the employment of a 5 per cent solution of brucin for the production of local anesthesia, see Therap. Gaz., 1886, 173. Blinte and Moral's Local Anesthetic. — Biinte and Moral (Deut. Monats. f. Zalmheilk., 1910, No. 2) proposed the two following solu- tions for local anesthesia in dental practice: Novocain ad I 1.50 II 0.50 Sodium Chlorid . . . 0.92 0.92 Thymol 0.02 0.02 Distilled water 100.00 100.00 718 ANESTHESIA Solution I is for adults and solution II for children. One drop of suprarenin (1: 1,000) should be added to each c. c. before use. Butyl-chloral Hydrate (Trichlorbutylidene glycol). — Proposed by Liebreich in 1870 as a remedy for trigeminal neuralgia. In medicinal doses it produces deep sleep with cranial analgesia. Butyl Chlorid. — This compound was introduced as an anesthetic by B. W. Eichardson in 1869. He reported {Sci. Am. Suppl., ISTo. 515, 8227) that its physiological properties are practically identical with those of amyl chlorid {q. v.), and that its anesthetic value is practically the same as for amyl chlorid. The committee of the British Medical Association stated that, when butyl chlorid was administered to rabbits, it affected respiration, although not very rapidly. Butyl Hydrid. — This compound, introduced by B. W. Eichardson in 1867, was found by him to have the same physiological properties as amyl hydrid (g. v.), but the action was more rapidly developed. As re- gards its anesthetic value, this was found to be the same as for amyl hydrid, but, being a gas, it was found to be less practical for adminis- tration (see Eichardson: Sci. Am. Suppl., Nov. 14, 1885, No. 515, 8227). Calcium Guaiacol Sulphonate. — See Guaiacyl. Camphor Phenylated (Camphora carbolisata; Phenol Camphor). — A local anesthetic, used chiefly in dental practice. For the physical properties of phenol camphor, consult Lemberger, Therapie die Gegenwart, 1906, No. 5; Przeglad lekarshi, 1906, No. 23; and Pliarm. Ztg., 1906, No. 38. Camphorated Salol. — See Salol Camphor. Canadol. — A very light petroleum ether ("light ligroin") of the spe- cific gravity 0.650-0.700 ; a local anesthetic used by spraying. Caprylic Hydrid. — The experiments of Eichardson upon animals showed that this compound produced a long period of preliminary ex- citement, accompanied by vomiting. Anesthesia thus induced was very evanescent. Carbolic Acid. — Phenol has found use as a local anesthetic. Like creosote, phenol is popularly employed to inhibit toothache; indeed, it seems that all phenols containing at, least one free hydroxyl group are anesthetic. However, their use is very limited, owing to their caustic action. Moreover, carbolic acid does not penetrate deeply. Barwell {Archiv. Internal, de Laryng., 1907, No. 3) described a so- lution containing carbolic acid, 10 parts by weight; lactic acid, 50 parts by weight; and formaldehyd, 7 parts by weight, for the treatment of tuberculous laryngitis. It was said to have an anesthetic as well as a curative efl'ect. On carbolic acid as a local anesthetic, consult the following contri- butions : A LIST OF ANESTHETICS 719 Bericht d. K. K. Kranlcenansialt Rudolphstiftung in Wien, 187G, 293. Bill: Am. J. Med. Scl., Oct., 1870. Caspar!: Z. klin. Med., 1883, 537. Pirri: Lancet, Sept. 19, 18G7. Eae: Am. J. Med. Sci., 1870, 573. Eichardson : Deut. med. Woch., 1891, 1161. • Smith : Med. Rec, 1872. Walser: Mitteilungen des Vereins der Arzte SteiermarJcs, 189G, No. 4. Van der Weyde : Phila. Med. Surg. Rec, Aug., 1868. Carbon Dioxid. — A mixture of limestone and vinegar was used by the Romans as a local anesthetic (Pliny) ; Hickman proposed, in 1828, that it be used for inhalation (for a full account of Hickman's work, see pp. 5-7) ; and it was used by Snow in 1848. B. W. Eichardson used carbon dioxid as an anesthetic in 1852, and it had been also tried by ISTunneley three years earlier. Eichardson (Sci. Am. Suppl., No. 515, 8227) found that air containing 25 per cent of carbon dioxid produced rapid insensibility; that the insensibility was deep, with convulsive action, asphyxia, and reduction of temperature. He pointed out that its anesthetic action had not been investigated fully, but that death probably resulted from asphyxia, with the respiration failing primarily and the muscular irritability becoming rapidly ex- hausted; the after-effects of recovery were stated to be neither very pro- longed nor severe from deep anesthesia. Ozanam used a mixture of 75 parts of carbon dioxid with 25 parts of air in an operation upon a young man for the removal of an abscess. Malan (Gazzetta degli espedali e delle cUniche, 1910, No. 105) used solid carbon dioxid to produce anesthesia by cold; he found the anes- thesia ■ sufficient and deeper than that produced by ethyl chlorid. Gottheil (/. Surg., 22, 7; N. Y. Med. J., July 3, 1909) used solid car- bon dioxid as an anesthetic cauterant. See also : Serano-Nouell : Monatsli. f. praJct. Dermatol., 50, No. 7. Pusey : Monatsli. f. praht. Dermatol., 51, No. 7. Macleod : Brit. Med. J., 1910, No. 2561, 254. Fabry and Zweig: Miinch. med. Woch., 1910, No. 13. Klotz: Berl. klin. Woch., 1910, No. 48. On the inhalation of a mixture of carbon dioxid and oxygen as an auxiliary to chloroform anesthesia, see Levi: Rivista critica di clinica medica, 1910, 465; Crescenzi: Klin.-tlierap. Woch., 1910, No. 40, 960; Marchetti : Ibid., 961. Carbon Disulphid. — Although Nunneley introduced carbon disulphid for complete anesthesia in 1849, it has only found employment as a local anesthetic. Simpson found carbon disulphid to be a rapid and powerful 720 ANESTHESIA anesthetic, but disadvantageous. It was also tried by Harold Thanlow in 1850, B. W. Richardson in 18G8, Hermann, Miller, Serre, and others. On the physiological action of carbon disulphid, see the following: Delpech: "Memoire sur les accidents que developpe chez les ouvrieres en caoutchouc du sulfure de carbone en vapeur," Paris, 1865. For a discussion of the investigations of Delpech, see Chem. News, 1863, 216; Bernhardt: Ber. Idin. Woch., 1866, No. 32; Husemann: Jahresher., 1872, 495; Yermorel: "Le sulfure de carbone, ses proprie- tes, sa fabrication, moyens pratiques de verifier sa purite,'^ Tours, 1886. Richardson (Sci. Am. Suppl., No. 515, Nov. 14, 1885, 8227) re- ported that, when perfectly pure, carbon disulphid is of a pleasant ethereal odor, and free from pungency; that the quantity required for anesthesia was 4 to 8 fluid drachms; that the quantity of vapor in air was 10 per cent ; that anesthesia Avas very rapid, being produced in from three to five minutes with a brief spasmodic stage; that recovery was rapid and complete, with few bad effects; and that the reduction of body temperature under deep anesthesia was 2° F. He stated then (1885) that its anesthetic value was yet undetermined, but that from experiments on inferior animals it seemed to be safe. To quote Rich- ardson, "Death in the vapor is gradual, the circulation outliving the respiration. In one animal, a dog, author observed life return, spon- taneously, after respiration had ceased for seven minutes." Workmen in caoutchouc factories, wherein carbon disulphid is em- ployed as a solvent, sometimes develop toxic phenomena, as headache, giddiness, deafness, amaurosis, and occasionally paraplegia. It would seem to be demonstrated that carbon disulphid is a powerful poison, the direct action being narcotic. It may be mentioned here that the xanthates have a similar action to carbon disulphid, and it is said that a general narcosis can be effected in man by them; this is as one would expect since the xanthates arc readily decomposed into alcohol and carbon disulphid. Carbon Monoxid. — Nunneley proposed carbon monoxid as an anes- thetic in 1849. Snow, Herapath, and Richardson experimented with it in 1852. Although dangerous to the human economy, it was used on lower animals by Richardson. He reported that 5 per cent of carbon monoxid in air caused rapid anesthesia, with convulsive action, and a fall of temperature at 2° F. under deep narcotism. The gas is a cumula- tive poison. Carbon Tetrachlorid. — A. Sansom and Protheroe Smith {B. and F. Med. Chir. Rev., 1867, 551) introduced "chloro-carbon" for inhalation in 1867; however, it has been but little used for this purpose, although it has been employed as a local anesthetic. Richardson (Sci. Am. Suppl., No. 515, 8227) stated that the quan- tity of carbon tetrachlorid required for complete anesthesia was 4 to 8 A LIST OF ANESTHETICS 721 fluid drachms; that the required change of air by vapor was 5 to 10 per cent; that the anesthesia was very slow and prolonged when in- duced, and that the convulsive stage was long and acute. He reported that its anesthetic value was indifferent, the action being too slow and the recovery too prolonged; the temperature was found to be reduced 4° F. during deep anesthesia. See, also, Simpson: Med. Times and Gaz., Dec, 1865; Lancet, June, 1867. Carbon tetrachlorid is said to act much more slowly and persistently than chloroform. It is usually stated to be a more powerful heart de- pressant (Simpson, loc. cit.), but Cushny describes it as only half as powerful as chloroform. Marshall found that the differences in action between carbon tetrachlorid and chloroform were mainly due to its physical characteristics. It is, however, more toxic and more irritating to the mucous membrane of the trachea and bronchi. It has been used by hairdressers to clean the hair, and a case of accidental poisoning owiiig to the inhalation of the vapor is recorded in the Lancet, 1907, 1, 1725 ; this case very nearly had a fatal termination. There is record of a fatal case in Paris. -' According to the investigations of Lehmann {Chem.-Ztg., 1906, No. 29, 330), the anesthetic action of benzin (see Benzene) is quantita- tively greater than that of carbon tetrachlorid. On the physiological action of carbon tetrachlorid, see the follow- ing: Andrews: Chicago Med. Exam., Dec, 1867. Bianchini: Stazione Sperimentale Agraria Italiana, 1904, 171. Freyss: CJiem.-Ztg., 1903, 1137. Haller: Bericht iiber die Weltausstellung im Paris, 1900. Morel: Compt. rend., 1877, 1460. Eegnauld: Ihid., 1885, 1146. Schwartz: "Handbuch zur Erkennung, Beurteilung und verhutung der Feuers- und Explosionsgefahr chemisch-technischer Stoffe und Be- triebsanlagen," 1902, 284. Caustica. — A, White : Arsenic acid, 0.001, morphin hydrochlorid, 0.0005; and cocain hydrochlorid, 0.0005. C, Black: Cobalt, 0.003; morphin hydrochlorid, 0.0005; and cocain hydrochlorid, 0.0005. For application in teeth cavities. C. E. Mixture. — An anesthetic mixture of 2 parts of chloroform and 3 parts of ethyl ether. Schiifer and Scharlieb (Travis. Roy. Soc. Edinburgh, J^l, ii, No. 12) have shown that C, E. Mixture is based upon the wholly fallacious theory that alcohol in the A. C. E. Mixture is merely a menstruum, and that ethyl ether in the C. E. Mixture exerts a stimulating action on the circulation. Ceratum Odontalgicum. — This toothache paste is composed of wax, chloral hydrate, camphor, and thymol ; it is also known as dontocerat. 722 ANESTHESIA Chelen or Chelene.— A "purified" ethyl chlorid. See Kelene. Chevanne's Local Anesthetic. — The followicg anesthetic has been proposeu by Chevanne for mucous surfaces without cocain: Phenol, 30 gr. ; menthol, 30 gr. ; quinin hydroehlorid, 24 gr. ; and adrenalin, l/12th gr. See Pharm. J., 32, 820. Chevanne states that this solution has no caustic action and that it is better than urea-quinin solution (Klin.-tlierap. Woch., 1910, Xo. 50, 1253; Rev, Hebd. de Laryng., 1910, 305). Chlorsethofonn. — Chloroform containing 0.25 per cent of ethyl chlo- rid. See Chem. and Drug., 1904, 1289. Chloral (Chloral Hydrate). — Forne stated that the administration of chloral hydrate in connection with the inhalation of chloroform pro- duced an effect upon the patient which very closely resembled the ef- fects produced by the combined use of morphin and chloroform. In a discussion of this affirmation before the Chirurgical Society of Paris, Dolbeau and Demarquay insisted upon the dangers attending such a combination. Kappeler made trial of the combination of chloral hy- drate with ether; though rather less disagreeable than the association of morphin with ether, there was very little to recommend this mode of inducing anesthesia. On a case of death from the effects of chloral and ether, see Morton and Lewis: Am. J. Med. Sci., Oct., 1876, 415. This narcotic may produce complete surgical anesthesia. It was used intravenously for a short period in the middle of the last century, and major operations have been performed under its influence. The dosage had, however, to be too high for the complete safety of the pa- tient. Chloral hydrate was fo\md by Delbet and Dupont (Rev. de Chir., June 10, 1910; Klin.-therap. Wocli., 1910, 682) to possess advantages over even scopolamin for commencing chloroform anesthesia. They re- ported on 850 cases of chloroform anesthesia in which chloral hydrate was employed. On chloral hydrate as a veterinary anesthetic, see Eehse: Monatsh. f. pralct. Tierlieilk., 21, 413; Berl. tierdrztl. Woch., 1911, 77. Chloral-acetone Chloroform (Chloran). — It has been said that the use of acetone-chloroform (see Chloreione and Meihaform) as a hyp- notic and local anesthetic is somewhat limited, owing to its insolubility in water, dilute alcohol, and its burning taste (Coblentz: "The Newer Eemedies," 4th ed., 33). It has been found that molecular quantities of chloral hydrate or chloral and acetone-chloroform condense, affording a compound which is said to be soluble to the extent of 1 per cent in cold water, very soluble in weak water-alcohol solutions, and free from burn- ing taste. The combination possesses the following formula: ^^^^^2^\0.CH(0H).CCL It forms fine feathery needles, melting at -|- 65° C, and having a cam- A LIST OF ANESTHETICS 723 phoraceous odor. It is said to be a prompt hypnptic and to have local anesthetic properties. Chloral-acetone chloroform is manufactured by a Swiss firm. Chloralamid. — See Chloralformamid. Chloralformamid.— This compound, CCl3CH(0H).C0NH2, also known as "chloralamid" and "formamidated chloral," is said to be an uninjurious hypnotic and analgesic; its action is less harmful than that of chloral, but it has less hypnotic power. Chloralformamid forms lus- trous, colorless crystals, melting at -f- 114-115° C. It is decomposed at higher temperatures and by wajm solvents. It slowly dissolves in 20 parts of water, and, at -|- 25° C, in 1.3 parts of alcohol. Chloralimid. — Trichlorethylidenimid, CCI3.CH :NH, is prepared from chloral-ammonia by means of heat or from hydrated chloral by ammonium acetate. It forms colorless crystals which are tasteless and odorless; it possesses a melting point of -|- 155° C, and is readily solu- ble in alcohol, ethyl ether, chloroform, and oils, but is only sparingly soluble in water. Chloralimid is employed both as a hypnotic and an analgesic. Chloral-menthol (Mentholated Chloral). — This preparation has been used as a local anesthetic in facial and other neuralgias. Chloral-orthoform. — Amido-oxybenzoic esters combined with chloral have been found to act as local anesthetics and antiseptics. Chloral-orthoform occurs in yellow crusts, sparingly soluble in wa- ter, but readily soluble in warm alcohol and in ethyl ether. When it is warmed with diluted inorganic acids, chloral is produced. Chloralose. — Chloralose (Alphachloralose; anhydroglucochloral) forms colorless crystals, possessing a bitter, disagreeable taste, and hav- ing the composition CgH^iClgOe. It is soluble in alcohol and in 200 parts of water; it melts at -1- 185° C. Chloralose is known chiefly as a hypnotic, but Kshishkovskii (Zentr. Physiol., 25, 8) found that when it was injected intravenously (0.07 per kg.) it produced in ruminants, in 15 to 20 minutes, a deep sleep, which lasted from 5 to 6 hours, with no ill effects. The anesthetic action was especially good in sheep (5 ex- periments), but not so satisfactory in rabbits and cats (4 experiments). When administered per os or per rectum^ it was found to be less effec- tive. Chloramyl. — Chloroform, one pound, mixed with 2 drachms of amyl nitrite (q. v.). Chlorbutane. — This compound has been employed for producing total anesthesia. See Butyl Chlorid. Chlorbutanol. — See Chloretone and Methaform. Chlorbutol. — A synonym for Chloretone (q. v.). Chlorethyl. — See Ethyl Chlorid. Chlorethylidene. — See Ethylidene Chlorid. 724 ANESTHESIA Chlorethylene Chlorid. — See Ethylene {Monocliloro-cMorid), Chloreton or Chloretone (Acetone chloroform; chlorbutanol ; "Ane- son"; "Anesin"). — This preparation is the tertiary trichlorbutyl alcohol [110.0(0113)20013], and is used as a local anesthetic and internal hyp- notic. It forms white acicular crystals possessing a taste resembling that of camplior. It dissolves sparingly in water, but more freely in al- cohol and glycerin. Acetone chloroform was discovered in 1881 by Willgerodt, and its solution (see Anesin) is said to produce no local irri- tation and no toxic symptoms. Because of the insolubility of chloretone in ordinary aqueous liquids or exudates, the local anesthetic effect de- velops very slowly, and consequently the substance cannot be compared with cocain hydrochlorid for rapidity of action. The manufacturers do not lay any stress whatsoever upon the effect of chloretone as a rapid-acting local anesthetic, but do commend it very highly as a seda- tive and hypnotic (Kossa, in 1893, found acetone-chloroform to have anesthetic and narcotic properties), and also for its power of preventing the growth of bacteria or fungi. A practical objection to the use of chloretone is that the toxic and therapeutic doses are too nearly alike, but it may be employed in small doses to produce local anesthesia. See Anesin; but on crystalline acetone-chloroform, a 1 per cent water solution of which constitutes anesin, see the following : Willgerodt: Ber., 1881, 2455; Willgerodt and Gemeser: J. praM. Chem., (2), 37, 362. Houghton and Albrich: J. Am. Med. Assn., 1899, 77 Lyon: P/iarm. J"., 1901, No. 1609, 521. Cappelletti: Riforma medica, 1901, ISTos. 277 and 278. Wheder: Lancet, 1903, No. 4148, 615. Fawcitt : lUd., 1903, No. 4149, 687. Bickle: Therap. Gaz., Oct., 1902. Wynter: Lancet, 1907, No. 4361, 879. Fiocre : Presse med., 1907, No. 58, 460. De Boter: Rev. Barcelonesa d. enferm. de oido, 1907, No. 9. Martinet: Therap. Monatsh.,. 1908, 115. Wargnier : These de Lille, 1908. Leyden: Med. Klinik, 1910, No. 52. Friedeberg: Deut. med. Woch., 1910, 9. Jenny-Berne : Therapie der Gegenwart, Aug., 1911, 13, No. 8. Welsh: Lancet, 1911, No. 4582. See Methaform. Chloriden. — See Ethylidene Chlorid. Chlorocarbon.— See Carbon Tetrachlorid. Chloroform. — See Ohapter VII. Chloroform- Acetic Acid. — Fournier {Compt. rend., 53, 1066) used a mixture of chloroform and glacial acetic acid as a local anesthetic. A LIST OF ANESTHETICS 725 Chloroform-Ether-Menthol. — This spray for local anesthesia con- sists of chloroform, 10 parts; ethyl ether, 15 parts; and menthol, 1 part. The local anesthesia produced thereby is said to last from two to six minutes. Chloroformium Albuminatum. — See Cldoroformium Gelatinosum. Chloroformium Colloidale. — See Desalgin. Chloroformium Gelatinosum. — Prepared from a mixture of equal parts of fresh albumen and chloroform; used for applying chloroform locally. Chloromethane. — See Methyl Chlorid. Chloryl (Coryl). — A local anesthetic mixture consisting of methyl and ethyl chlorids; it is said to be milder in action than ethyl chlorid. Chloryl has also been used externally. Chloryl Anesthetic. — An "absolute ethyl chlorid" of Scottish manu- facture. Cloran. — See Chloral-Acetone Choloroform. Cocadrenal. — A sterilized solution of adrenalin hydrochlorid and cocain, used as a local anesthetic. Cocaethylin (Ethyl-benzoylecgonin). — A local anesthetic, like cocain in action, but milder. Cocain.- — The constitution of benzoyl-ecgonin-methyl-ester is ex- pressed by the formula: CH.COOCH3 CH.O(C6H6CO) CH2 It is well known as a producer of local anesthesia (Schraff, 1862), which is by far its most important physiological attribute from a prac- tical standpoint. Not only pain but all sensations are affected; for ex- ample, taste is abolished upon the application of cocain' to the mucous membrane of the mouth, and heat and cold are not felt. This local anesthetic action appears to be dependent upon the structure of the ecgonin nucleus, and upon the presence and relative positions of the two substituting groups, the alkyl and benzoyl radicals. Of these fac- tors, the presence of the benzoyl group seems to be the most important. The anesthetic property of cocain has been shown to be associated with its functions as an alkalamin ester. For an investigation of its recommended substitutes, see, among others, Le Brocq: Pharm. J., 82, 673; Brit. Med. J., Mar. 27, 1909, 783. On the results of a clinical study of cocain, stovain, tropacocain, 726 ANESTHESIA novocain, eucain, etc. {q. v.), see Piqnand and Dreyfus: J. physiol. path. gen., 12, 70. On the comparative toxicity and pharmacological action of cocain, stovain, anesthesin, novocain, alypin, and eucain-B, as de- termined by Chevalier and his students, see Bull. sci. pliarmacolog., 16, 518; cf. also Senator: Milnch. med. ^Yoch., 1910, ISTo. 10, 524. On the distinction between cocain and its substitutes, see Scher- batschev: Apoth.-Ztg., 21, 441. For a report of an investigation relating to combinations of cocain with other local anesthetics, see Leo Zorn: Z. f. exper. Path. u. Therap., 12, 529. Cocain-Alinninum Citrate. — This product of a patented process is employed as an astringent and local anesthetic; it is a compound of 1 molecule of aluminum citrate with 1 molecule of cocain. Cocain and Adrenalin Ointment. — An ointment said to contain co- cain hydrochlorid, 2 per cent; solution of adrenalin chlorid, 17 per cent; hydrous wool fat, 25 per cent; white petrolatum sufficient to make 100 per cent. Put up in collapsible tubes for application to the eye. Cocain Arabinate. — This salt was introduced by Erhardt as a suc- cedaneum for the hydrochlorid, especially for lumbar anesthesia. It is said to be absorbed much more slowly and it is reported that its anes- thetic effect lasts three times as long as that of the hydrochlorid; more- over it has been recorded that it scarcely disturbs the nervous system. Cocain-Ethyl (or Methyl) Chlorid.— In Eng. Pat. 10,594, 1897, the claim is made for the production of local anesthetics by means of solu- tions of cocain in liquids boiling below -|- 30° C. Cocain Benzoate; Cocain Borate; Cocain Formate. — Employed as local anesthetics. Cocain borate (68.7 per cent cocain) solutions are more permanent than those of the hydrochlorid. Cocain Hydriodid. — Marcus (Ber. Hher Verhandlung Central-Ver- eins. Deut. Zahndrzte, 1897, 409) proposed the employment of "cocainse hydroiodidas" in dental surgery as a substitute for cocain hydrochlorid as a means of producing electro-anesthesia. See, also, Mewes: Elek- trochem. Z., 1897, No. 3, 49. Cocain Hydrobromid; Cocain Hydrochlorid. — Employed as local anesthetics. Cocain Lactate. — A dental anesthetic. It is a thick, white liquid, soluble in water and alcohol. Cocain Nitrate ; Cocain Oleate. — Employed as local anesthetics. Co- cain oleate is a 5, 10, 15, 25, or 50 per cent solution of cocain in oleic acid, soluble in alcohol and oils. Cocain Phenate (Phenol-Cocain; Cocain Carbolate; Cocain Pheny- late). — Veasey {Med. News, 1893, 345) states that cocain phenate in a 2 per cent solution in alcohol and water acts excellently as a local anes- A LIST OF ANESTHETICS 727 thetiCj while it does not produce the unpleasant secondary effects caused by cocain hydrochlorid. It also possesses an antiseptic action. Cocainum Phenylicum Merck-Oefele. — A honey-yellow mass of but- ter-like consistency with crystals distributed throughout; it is insoluble in water, and is slightly soluble in alcohol and ether. It possesses the composition 0^71121^04. CeHjOH. It is used as a local anesthetic in dental operations. Cocainum Phenylicum Poisnot. — A mixture of 2 parts of cocain, 1 part of phenol, 20 parts arachis oil, and 40 parts paraffin oil, supplied in 1-gm. tubes. Cocainum Phenylicum Vian. — A mixture of phenol with cocain hydrochlorid. Cocain Spray. — Oocain hydrochlorid, 0.12 part; menthol, 0.24 part; oil of eucalyptus, 0.3 part; camphor, 0.48 part; and 28.5 parts of a mix- ture of 2.5 parts of Peru balsam with 100 parts of rectified petroleum. Cocain Tartrate. — A local anesthetic, the uses and dosage of which are the same as for cocain hydrochlorid. It is a white, crystalline pow- der, soluble in water and alcohol. Cocain-Urethane. — By the action of chlorformic ester on the amido- derivative of cocain, Oocain-Urethane, (COOC2H5)NH— CH CH.COOCH3 CH.OCCfiHsCO) CH,, is produced. This is said to be a strong anesthetic, acting on the liver in a characteristic manner and giving rise to toxic symptoms. Cocainol. — A Berlin firm has placed various forms of this external remedy on the market; these all contain anesthesin (Eitsert's), but no cocain. Among the forms are : Oocainol-menthol drops, cocainol tab- lets, and cocainol drops. The latter contain 0.2 gm. of anesthesin each. Hemostatic cocainol bougies contain 10 per cent of anesthesin and 0.0001 gm. of suprarenin; there are also listed cocainol bismuth tablets, cocainol quinin tablets, cocainol condurango tablets, and cocainol sano- form dusting powder. See Pharm. Ztg., ^7, 916. Cocainolbalsam, Schmerzstillender. — This salve contains vaselin, menthol, methyl salicylate, and anesthesin. Cocainol-Creme. — This contains anesthesin, aluminum beta-naph- tholdisulphonate, zinc acetate and thymol (Chem. Centr., 1909, ii, 1584). According to Oelie's Codex (Xov., 1910, 311), sanovagin (cocainol- creme) is "a combination product of anesthesin with B-naphtholsulphon- 728 ANESTHESIA ate of aluminum-zinc acetate, methyl cTi-iodosalicylate, mercury oxycy- anid, and thymol.'' It is used in the treatment of genito-urinary dis- eases, especially those of the female organs. Cocainol-Lbsungen. — Sterilized solutions of 0.7 per cent subcutin dissolved in .water, Cocainum Arabinicum. — Employed in lumbar anesthesia. See GunimitropaJiokain. Co-Capsulin. — This anesthetic and hemostatic contains alcohol, 2 per cent; cocain, 0.5 per cent; and supracapsulin, 1:2000. Codrenin. — Two forms of this preparation, which is used as a local anesthetic and hemostatic in dentistry, are offered, of different strengths, in ounce bottles, namely: "A" — Each fluid ounce contains: Cocain hydrochlorid (2 per cent) 9 1/5 grs. Adrenalin chlorid (1 :15,000) 1/36 gr. Chloretone 2 1/4 grs. "B" — Each fluid ounce contains: Cocain hydrochlorid (1 per cent) 4 3/5 grs. Adrenalin chlorid (1 :5,000) 1/12 gr. Chloretone 2 1/4 grs. The chloretone is said to be added not because of any local anes- thetic effect, but specifically to prevent the growth of fungus. Eor this purpose it is said to have been found to be most efficient, more so, in fact, than all of the preservatives known in solutions of the alkaloids or similar substances employed hypodermatically. Cold. — On the production of local anesthesia by means of refrigera- tion or cold, see the following contributions : Arnott: "On Cold as a Means of Producing Local Insensibility," La7icet, 1848, 3, 98, 287. Bailly: "Kouveau precede de refrigeration locale par le chlorure de methyle," Gaz. lield., 1888, No. 5. Baudouin: "Chlorure d'ethyle comme anesthesique locale," Progres mU., 1892. Berger: "Bromathyl als Lokalanastheticum," Breslauer drztl. Z., 1883, No. 8. Bernard: "Anesthesie locale par le sulfure de carbone," Gaz. med., 1874, 27. Bigelow: Gaz. liebd., 1866, No. 23. Bloch. "Om Indskrankning i Anvendelse af Inhalationsanasthesi," NordisU med. Arhiv, 1899, No. 33 ; BiUiotheh for Laeger, 1898. Boeri and Silvestro: "Sur la mode de se comporter des differentes sensibilites sous faction des divers agents," Archiv. Ital. d. Biol, 31, 460. A LIST OF ANESTHETICS 729 Braatz: "Zur Lokalanastliesie/' Zeniralbl. f. Chir.,, 1895, No. 2G. Bumm: "tJber lokale Anasthesierung," Wiener Klinilc, 1886. Cardenal: "Une decouverte de Dr. Letaraendi sur I'anesthesie lo- cale/' Archiv. d. physiol. norm, et pathoL, 1875, S, 769. Debove: "Traitement de la sciatique par la congelation/' iSociete med. des hop., Aug., 1884. Delcominete : Gaz. des hop., 1866, No. 45. Ehrmann: "Athylchlorid als Lokalanastheticum in der Dermato- therapie/' Wiener med. Woch., 1893, No. 26. Feiber: "Chlormethyl als lokales Anastheticmn/' Berl. Iclin. Woch., 1889, No. 5. Fratscher: "^Kontinuierliche und langsame Nervenreizung," Jena. Z. f. Naturkunde, 11, 481. Galeezowski : "De I'anesthesie locale dans la chirurgie oculaire," Eec. d'ophthal., 1876, 93. Ganz : "tJber Athychlorid," Therap. Monatsh., 1893, 113. Gendre: Einfluss der Temperatur auf einige tierisch-elektr. Er- scheinungen," Pfliigers Archiv, 3J/., 423. Giraldes : "Anesthesie chirurgicale," in "Nouveau dictionnaire de medecine et de chirurgie," Paris, 1865. Girard: "Zur Erleichterung der Lokalanasthesie," Zentralbl. /. Chir., 1874, No. 3. Griitzner: "tJber verschiedene Arten der Nervenerregung/' Pflii- gers Archiv, 17, 315. Guerard: Gaz. des hop., 1854, 88. von Hacker: "Zur lokalen Anasthesie," Wiener hlin. Woch., 1893. Hattyasi: "Yersuche mit Athylchlorid/' Pester med. Chir. Presse, 1893, No. 33. Heinzmann: "tJber die Wirkung allmahlicher Anderungen ther- mischer Beize," Pfliigers Archiv, 6, 333. Herzog: N eue Zeitung filr Mediziii, 1S50. Husemann: Virchow-Hirsch Jahre., 1866, 1, 344; 1867, 1, 501. Illich : Med. Ztg. Russlands, 1853, No. 55, and 1853, No. 15. Kiimmell: "Uber Narkose und lokale Anasthesie," Festschr. z. SO jdhr. Stiftung. des drztl Vereins, Hamburg, Leipzig, 1896. Lauenstein: "Die lokale Anasthesie durch Ather," Zentralbl. f. Chir., 1880, 497. von Lesser: "Demonstration zur lokalen Anasthesierung/' Deut. Chir., 1881. Letamendi: "Un pas vers la resolution du probleme de I'anesthesie. locale," Barcelona, 1895. Letang: "Note sur un nouveau procede d'anesthesie locale," These, Paris, 1894. ^xxm.: Lancet, Aug., 1850. 730 ANESTHESIA Eedard: "Chlorathyl als Lokalanastheticum/' La sem. med., 1891, 133. Eichardson: Med. Times, 1866. Eichardson and Greenhalgh: Med. Times, 1866. Eichet: "Anesthesie localisee/' Gaz. des Hop., 1854, 251, 263, 267; Bull, de la Soc. de Chir., J/., 519. Eosenthal: "Experimentelle und praktische Beitrage zur Einwirk- ung der Lokalanasthesie auf das Nervensystem," Osterr. Z. f. Heil- hunde, 1867, 373. Eossbach: "Eine neue Anasthesierungsmethode des Kehlkopfs,^' Wiener med. Presse, 1880, No. 40. Eottenstein : Tagehlatt d. Versammlung deut. Natur. u. Arzte in Frankfurt a. M., 1867, 43. Scheller: "Eeines Athylchlorid als ortliches Anastheticum und An- tineuralgicum," Deut. Monats. f. Zahnheil., 1891, No. 5. Simonin: Gaz. Med. de Paris, 1866, jSTo. 11. Terillon: "Anesthesie locale et generale produite par le bromure d'ethyle,"' Gaz. Med. de Paris, 1880, No. 22. Velpeau : Bull, de V Academie de Med., 15, 85. Warren: "Surgical Observations," Boston, 1867. Wells, Spencer: Med. Times, 1866. Wiesendenger : "Fliissige Kohlensaure als Lokalanastheticum," J. f. Zahnheilk., 1891, No. 21. Wittmeyer : "tJber Anasthesie," Deut. Klinik, 1852, No. 19. Compound Anesthetic Ether. — A mixture of equal parts of absolute ether and amyl hydrid (rhigolene) (Eichardson, 1868). Eichardson (Sci. Am. Suppl., No. 516, 8240) states that this mix- ture possesses a density of 0.672 and boils at -[-90° F. He found that it is pleasant to breathe and that it is a rapidly acting anesthetic, but that it is dangerous, causing death in the lower animals, suddenly, from cardiac paralysis. "It is not recommendable as a general anesthetic, and has once been a cause of death in man. For producing local an- esthesia from cold in the form of a spray it is good and is generally em- ployed" (1885). Compressed Lozenges Orthoform, 1 g^^ain. — Each lozenge contains orthoform (q. v.), 0.065 gm. (1 grain). Compressed Tablets Anesthesin, 2y2 grains. — Each tablet contains anesthesin (q. v.), 0.162 gm. (21^ grains). Conephrin. — A solution containing cocain and paranephrin, used as a local anesthetic. Corona. — This is a local anesthetic, put on the market by a Leipzig firm, claimed to consist of a solution of less than 1 per cent of cocain in distilled water, with the addition of picric acid, nitric acid, oils of wintergreen, thyme, mentha arvensis, and eucalyptus, and benzoic and A LIST OF ANESTHETICS 731 boric acids. It is employed in painless dentistry. It is stated in Gelie's Codex (Nov., 1910, 88) that "corona" contains, besides coeain, nitric acid, picric acid, potassium hydroxid, oils of gaultheria, baptisia, thyme, mentha arvensis and eucalyptus, benzoic acid and boric acid, in water solution. Coryl. — See Chloryl. Coryloform. — An anesthetic mixture containing ethyl chlorid, methyl chlorid, and ethyl bromid. See Pharm. Ztg., 53, 817. Coumarin. — Ellinger (Archiv exper. Pathol. Pharmakol., 1908, Suppl.) found that in frogs injections of 0.03 to 0.05 gm. of coumarin, the anhydrid of coumaric acid-, caused deep anesthesia of the nervous centers in the brain and spinal cord, extending to the vagus and the respiratory center, while the vasomotor center was not paralyzed and the functions were not demonstrably altered. In rabbits injections of 0.15 to 0.2 gm. per kg, body weight produced deep anesthesia lasting about 10 minutes. He concluded that coumarin was a harmless anesthetic when properly administered, and that it was not a dangerous cardiac poison as claimed by Kohler (Zentr. f. d. med. Wissenschaft., 1875, 867 and 881). Cianci (Giornale Internaz. delle Sci. med., 1908, Nov.) ascribed to coumarin an action resembling that of camphor. Creme Dehne. — A salve of the following formula : Extr. Hamamel. destill 30.0 aa 5.0 Acidi borici ) Anesthesin Ad. Lanae c. aqua 55.0 Camphor. Essent. Heliotrop. - aa 1.0 Essent. Eosemar. Creosote. — Used in dentistry, as a local anesthetic. See Carholic Acid. Cycloform. — This compound is the isobutyl ester of para-amido- benzoic acid; it is a white crystalline powder, melting at -f- 65° C, sparingly soluble in water, but readily soluble in alcohol and ether. Impens (Therap. d. Gegenwart, 1910, No. 8) showed that cycloform has the advantage that it dissolves in water only to the amount of 0.023 per cent; this sparing solubility leads to an entirely local action and prevents symptoms due to absorption. Impens found the anesthetic action of cycloform to be very great. On cycloform, see also: Krecke : Milnch. med. Woch., 1910, 2447. Most: Heilkunde, 1910. Strauss : Milnch. med. Woch., 1910, No. 50, 2643. Wyss: Archiv f. Verdauungs-Krankheiten, 16, No. 4. 732 ANESTHESIA Werner : Milnch. med. Wocli., 1910, No. 38, 2004. Zeller: Med. Klinilc, 1910, No. 45, 1748. Bircher: Idem, 1911, No. 6, 223. Rosenberg: Deut. med. Woch., 1911, No. 9, 409. Cycloform appears from these reports to be non-irritant, prompt and intense in anesthetic action. Cyclorenal. — A combination of cycloform, adrenalin, balsam Peru, and coryfin, made in Berlin, in the form of salves and suppositories for the treatment of rectal diseases. See Kretschmer : Berl. Min. Woch., 1911, J^8, 2168. Rabow (Chem. Ztg., 1912, No. 21, 190) states that cyclorenal is a local anesthetic. Bentesthin. — A dental local anesthetic containing in 1 c. c. of a physiological salt solution 0.005 gm. cocain hydrochlorid, 0.015 gm. novo- cain, and 0.05 gm. of synthetic suprarenin. See Pharm. Zentralh., 51, 1126. Dentalon or Dentalone. — This dental local anesthetic is a combina- tion of chloretone {q. v.) and several essential oils, and is used spe- cifically in the treatment of exposed nerves and decaying teeth. It has been found to be a very practical and satisfactory obtundent. ■ Each fluid ounce of dentalone contains approximately: Oil Cloves 300 min. Oil Birch 12 min. Oil Cinnamon 50 min. Chloretone 175 min. The label bears the information that dentalone is an admixture of the oils of cloves, cassia, and gaultheria, containing in solution 30 per cent of their weight of chloretone; that is 175 gr. of chloretone, and Oils of Cloves, Gaultheria, and Cassia {q. v.), to each fluid ounce. Dentola. — This contains cocain, 1 ; potassium bromid, 10 ; glycerin, 200; and water, 200. It is used in dentistry. Dentorol. — "Eugenol-para-chloro-chlorphenol-Menthol.'' It is used in dentistry. ' '■' Desalgin. — Schleich {TJierap. d. Gegenwart, 1909, 1, 138) succeeded in combining chloroform with an albumin and in procuring a definite compound with a fairly constant percentage of about 25 per cent of chloroform in the dry state. This preparation is a gray, amorphous, fine powder; it represents "colloidal chloroform'' in a solid state, and may find application in anesthesia. > '■' Dialkylaminoalkyl 3 : 4-Diaminobenzoates. — According to Einhom (German Patent 194,365), these compounds have considerable local an- esthetic properties. ■ ■ . - ; ; Dibromethane.^See Ethylene Bromid. A LIST OF ANESTHETICS 733 Dichlor ethane. — This ester, CIIg.CHCL, is said to have a similar action to chloroform. Dichlormethane. — See Methylene Chlorid. Dichlorpropane. — According to Brissemoret and Chevalier (Compt. rend., IJfS, 731), 2, 2— Dichlorpropane, CH3C(Cl2).CH3, is a fugitive anesthetic not to be considered the superior of ethyl chlorid. Diethylaminoethyl Benzoate. — This dialkylaminoethyl benzoate, de- scribed by Schering (German Patent 175,080), has been stated to have local anesthetic properties. Dimethylacetal (Ethylidene dimethyl ether), CH3CH(0CH3)2.— An anesthetic used in the place of, or with, chloroform. It is prepared from aldehyd, methyl alcohol, and glacial acetic acid by the action of heat. It forms a colorless liquid, soluble in water, alcohol, ether, and chloroform; the specific gravity is 0.879 at 0° C. and the boiling point -f- 62° to 63° C. See von Mering's Mixture. Dioform. — Dioform, or acetylene dichlorid, is a colorless fluid with an odor resembling that of ethyl chlorid and chloroform. Its graphic CH CI formula is (symmetrical 1.2-dichlorethylene). Its specific grav- CH CI ity is 1.29 and it boils at about -|- 55° C. Villinger {Archiv f. hlin. Cliir., 1907, No. 3 ; Zentr. f. Chir., 1907, No. 44, 1282; Odontol. Blatter, 1907, No. 17, 327) conducted some experiments with dioform on dogs with the view of ascertaining whether the narcotic action resembled that of chloroform. He produced nar- cosis lasting 10 minutes to 2 hours, and gave doses up to 125 gm. with- out observing any threatening symptoms. Sleep set in within 6 to 10 minutes, and was preceded by only a short stage of excitation. The re- flexes were completely abolished during sleep, while the strength and frequency of the pulse remained constant. The urine remained almost normal, so that there was no reason to suspect inflammation of the kidneys. The trials made by Villinger on human subjects also gave sat- isfactory results. 15 to 25 gm. of dioform were used; after about a minute, slight excitation was observed; after 3 minutes more, sleep ensued, to become deep sleep 5 minutes after the beginning of the an- esthesia. Pulse and respiration remained good, the patients awakened quickly, there was but slight tendency to vomit, and no albumin was found in the urine. However, systematic clinical study is required be- fore acetylene dichlorid should be used as a substitute for chloroform. Dionin.- — Dionin (ethyl-morphin hydrochlorid) is a white, some- what bitter powder fusing at -j- 123°-125° C; it is soluble in seven parts of water, one and one-half parts of alcohol, and twenty parts of syrup; it is insoluble in chloroform and ethyl ether. Dionin is pre- cipitated from its solutions by most of the alkaloidal reagents. 734 ANESTHESIA Dionin has been reported upon by a number of observers; it would seem that it shares the analgesic and hypnotic properties of morphin without producing the nausea, constipation, and other disagreeable after-effects of that alkaloid. However, it acts even more powerfully upon the respiratory centers than does morphin. According to The Dispensatory of the United States of America, 19th ed., 1473, it is, nevertheless, less decisive in its action than is morphin, so that in cases of severe pain morphin will bring relief after the failure of dionin. A 5 per cent solution of dionin has been used by ophthalmologists; it occasions immediate irritation and swelling of the conjunctiva, fol- lowed, in a short time, by a rapid subsidence of the swelling and a con- dition of analgesia and anesthesia. The employment of dionin in local anesthesia has been discussed by the following authors: Graefe: "Das Dionin in der Augenheilkunde," Deut. med. Woch., 1900, Therap. Beil., No. 2. Wolffberg: "Die Dioninophthalmie und ihre Bedeutung," Therap. Monatsh., May, 1900. Di-para-anisyl-monophenetyl-g^anidin hydrochlorid. — See Acoin. Dipropesin. — This seems {Apoth.-Ztg., 1908, 786; Yierteljahr. f. prak. Pharm., 1908, 305; Pharm. Ztg., 63, 817) to be a derivative of urea, containing two molecules of propesin {q. v.) bound together by a CO group: .NH CeHi COOCjHt / CO \ ^NH CsH* COOC3H7 Dipropesin is described as a white crystalline powder melting at -\- 171-172° C, tasteless and soluble in alcohol, but insoluble in water. It is said to develop its anesthetic action only in alkaline media, and to be therefore of use as an internal sedative in intestinal affections. Kluger {Therap. Monats., 1909, 76) published clinical reports on the use of dipropesin. He stated that dipropesin has no anesthetic effect until propesin {q. v.) is liberated in the alkaline body fluids. Dolonephran. — An anesthetic of German manufacture, said to con- tain alypin {q. v.), suprarenin, and sodium chlorid. Dolorant Tablets. — Each of these tablets of Swiss preparation is said to contain 0.0001 gm. of adrenalin, 0.01 gm. of cocain, 0.002 gm. of sodium chlorid. When dissolved in water, the solution is used in the painless extraction of teeth. Dolorant Tabletten.^ — Each tablet contains 0.00001 gm. adrenalin, 0.01 gni. cocain, and 0.00499 gm. sodium chlorid. One to four tablets are A LIST OF ANESTHETICS 735 dissolved in 1-4 c. c. of water for use in the production of loeal anesthesia in dentistry (Gehe's Codex, Nov., 1910, 100). Dolorifuge. — A mixture of creosote, 1 ; chloroform, 1 ; and ethyl acetate, 2. It is used in dentistry. Dontocerat. — See Ceratum Odonialgicum. Dutch Liquid; Elayl Chlorid. — See Ethylene Chlorid. Dysphagin. — No I. Tablets containing cocain, menthol, anesthesin, sodium biborate, and aromatics; No. II. The same, but without cocain; No. III. Anesthesin, citric acid, tannin, and aluminum acetate. Dysphagin is used in the treatment of angina and throat affections. Elayl Chlorid. — See Ethylene Chlorid. Electric Analgesia. — On Electric Analgesia and Sleep, see Chapter XVI. Enophthalmin. — The hydroehlorid of oxytouyl-methyl-vinyl-di-ace- tonalkamin, slightly soluble in water. Used, in 2 per cent solution, as an anesthetic in ophthalmology. Ensemin. — A solution of about 1 per cent cocain, containing, in addi- tion, adrenalin anfl chloretone. Used as a dental anesthetic. Epicain. — A solution containing cocain hydroehlorid and epinin (dihydroxyphenylethylmethylamin), marketed also as tabloid ophthal- mic epicain. Erhardt's Solutions. — These are solutions for lumbar anesthesia, con- sisting of salts of arabic acid with certain anesthetic bases, as cocain, tropacocain, stovain, novocain, etc. See German Patent 211,800 of 1908; and also Erhardt: Woch. f. Tierheilkunde, 1908, Nos. 27 and 28; Mimch. med. Woch., 1908, Nos. 19 and 26. Epsom Salts. — A saturated solution of magnesium sulphate has been employed as a dental local anesthetic; it is said to be very satisfactory. See Magnesium Salts. Erythrophlein Hydroehlorid, ErythrophlcEinum Hydrochloricum (Erythrophleinae Hydrochloras). — This salt of an alkaloid from the bark of Erythrophloeum guinense, Don. (sassy bark), is used as a local anesthetic in eye practice in 0.05 to 0.25 per cent solutions. It forms a yellowish-white amorphous powder, soluble in water and alcohol. Its solutions are not stable. On the physiological action of Erythrophlein Hydroehlorid, see Harnack: Berl. hlin. Woch., 1895, 759, On its em- ployment as a local anesthetic, see the following papers : Brandt: "Versuche mit Erythrophlaein bei Odontalgic/^. Therap. Monatsh., June, 1888. Guttmann : "Versuche mit Erythrophlaein," Berl. Tclin. Woch., 1888, No. 13. Hirschf eld : "Ueber Erythrophlaein," iUd., 1888, No. 11. Karewski : "Ueber die praktische Verwendbarkeit der Erythro- phlaein-anasthesie," ihid., 1888, No. 11. 736 ANESTHESIA Koller: "Erythrophlaein," Wiener klin. Woch., 1888, No. 6. Lewin: "Ueber das Hayagift iind das Erythrophlaein," \Rm; ZentralU. f. Chir., 1897, 317. Fraenkel : "Contribution a I'etude du broniure d'ethyle comme anes- thesique general," These, Paris, 1894. Garin: "Die Bromathylnarkose bei Zahnextraktion," Wratsch, 1900, No. 31. ZentralU. /. Chir., 1900, 1307. Geza Dieballa: "Ueber die quantitative Wirksamket verschiedener Stoffe der Alkohol — und Chloroformgruppe auf das Froschherz," Archiv f. exper. Path., 1894, S^, 137. Gilles: "Ueber Bromathylnarkose," Deut. Monais. f. Zahnheilk., 1889, 271, 347; "Beschreibung einer Bromathernarkose nebst weiteren Bemerkungen zur Bromathernakose," Deut. Monats. f. Zahnheilk., 1891, 9, Jt, 'Ueber Bromathylnarkose," Berl. Bin. Woch., 1892, Nos. 8-9, 166, 195. Givel : "De Femploi du broraure d'ethyle dans les accouchements naturels," Diss., Berne, 1881. Gleich: "Ueber Bromathylnarkosen," Wiener klin. Woch., 1891, 1002; "Ein Todesfall nach Bromathylnarkose," Wiener klin. Woch., 1892, No. 11, 167. Grunert : "Die Gefahrlichkeit des Bromiithers ist 200mal so gross als die des Stickoxyduls," Diskussionsbem., Gesellsch. f. Natur. u. Heilk. zu Dresden, 30 Marz, 1913. Mmich. med Woch., 1912, 1404. Giinzberg: "Ueber Bromathyl," Med. Kalenderj, 1891. Ref. bei v. Ziemacki, loc. cit., 731. Gurlt: "Zur Narkotisierungsstatistik," Yerh. d. XXIV Deut. Chirurgenkongr., 1895, Teil ii, 460. von Hacker: "25 Bromathylnarkosen, Anlage 12 zu Gurlts. Sta- tistik." Verh. d. XXI. Deut. Chirurgenkongr., 1892, Teil ii, 331. Hackermann: "Ueber die Anwendung des Bromathyls zur Narkose Kreissender" Gesellsch. f. Gehurtsh. u. Gyndk. zu Berlin, 1883; ZentralU. f. Gyndkol., 1883, 546. Hardy : "Bromathylnarkose in der Zahnheilkunde," Schweiz. Viertel- jahrs. f. Zahnheilk., 1898. Haffter : "Die Bromathylnarkose," Correspondenz-Blatt f. Schweizer Aerzte, 1890, 106, 143. Hagedorn: "Zirka 100 Bromathylnarkosen, Anlage 13 zu Gurlts. Statistik." Verh. d. XXI. Deut. Chirurgenkongr., 1892, Teil ii, 332. Hahn : "Die Narkose der Chirurgie und Zahnheilkund," Diss., 1896. Hammeeher: "Ueber Bromathylnarkosen," Deut. Monats. f. Zahn- heilk., 1889, 7. Verh. d. LXII. Vers. deut. Natiiruf. u. Aerzte zu Heidel- berg, 1889, 668 ; Korrespond. f. Zahndrzte, 1889, 343. A LIST OF ANESTHETICS 743 Hartmann et Bourbon : "Le bromure d'ethyle comme anesthesique general," Rev. de Chir., 1893, 13, 701. Haslebacher: "Experimentelle Beobachtungen iiber die Nachwir- kungen bei der Bromathyl. und Chlorathylnarkose," Diss., Berne, 1901. Heitmiiller : "Empfehlung des Bromathers," DisTcussionshem. Gesellsch. f. Natur. u. Heilk. zu Dresden, 30 Miirz, 1912. Milnch. med. Woch., 1912, 1403. Hennicke: "Vergleichende Untersuchungen iiber die Gefahrlichkeit der gebrauchlichten Inhalationsanasthetika," Diss., Bonn, 1895. Hoddes : "Ueber Bromathernarkosen," Diss., Freiburg i. B., 1892. Hollander : "Das Bromathyl in der zahnarztlichen Praxis," Verh. d. X. Internat. med. Kongr. zu Berlin, 1890, 5, 14, 57. Jendritza: "Ein Fall von Bromathylintoxikation/' Therap. Monats., 1892, 152. Kappeler : "Beitrage zur Lehre von dem Anastheticis," Arch. f. hlin. Chir., 1888, 37, 364; Bromathyl, 376. Kocher : "tjber kombinierte Chloroform- Ather-Narkose," Nachtrag : "Bromathyl-Ather-JSTarkose." Korrespondenz-Blatt. f. Schweizer Arzte, 1890, 590. -"Chirurgische Operationslehre," 1902. Empfehlung der Bromathyl- Ather-Narkose. Kohler : "Zur Bromathylnarkose," Freie Verein. d. Chir. Berlins, 2, 1893; Deut. med. Woch., 1894, Vereinsheilage, 7; Zentralbl. f. Chir., 1894, 41. Kolliker: "tJber die Anwendung der Bromathylnarkose in der chirurgischen Praxis," Zentralbl. f. Chir., 1891, 385. Krecke: "Beitrag zur ISTarkotisierungsfrage," Milnch. med. Woch., 1894, 806. Bromathyl. Kretschmann : "Anwendung des Bromathyls in der Ohrenkeil- kunde," Archiv f. Ohrenheilk., 1889. "Bericht iiber neuere Mittel in der Ohrenheilkunde," Archiv f. Ohrenh., 1889. Langgaard : "tJber Bromathyl," Therap. Monat., 1887, 62. Lanz : "Bemerkung zu der Mitteilung von Dr. Otto Zuckerkandl, TJber eine Modifikation des Chloroformiernes," Zentralbl. f. Chir., 1891, 969, Bromathyl, 972. Larisch: "1263 Bromathylnarkosen," Diss., Breslau, 1899. Laury: "872 Bromathylnarkosen, Anlage 24 zu Gurlts. Statistik." Yerh. d. XXI. Deut. Chir., 1892, Tail ii, 350. Lebert : "Des accouchements sans douleur ou de I'analgesie obstetri- cale par le bromure d'ethyle," Rev. med. de I'Est, 1882. Deut. Med., 1882, 250; Archiv de Tocol., 1882. Ref. bei Givel, 1. Lepmann : "Experimentelle und klinische Untersuchungen zur Frage der Bromathernarkosen," Berlin, 1895. Lesin : "tJber die gemischte Bromath}d-Chlorof orm-Xarkose," Y. Kongr. Arzte, St. Petersburg, 1894. Zentralbl. f. Chir., 1894, 982, 744 ANESTHESIA Levis : "The New Anesthetic, The Bromid of Ethyl," Phila. Med. Times, 1880, 188. Virchow-Hirsch : Jaliresler., 1880, 454. Lewin: "-Nebenwirkungen der Arzneimittel," Berlin, 1893. Lohers: tJber den Einfluss des Bromathyls auf Atmung und Kreis- lauf," I>iss.^ Berlin, 1890. "Sitzung der Phj^siol. Gesellsch. zu Berlin," 9. Mai, 1890, Zit. Nach Koclier. ( Kaninchenversuche mit Bromathyl- narkose.) Lowenstein: "Empfehlung des Bromathers fiir kurzdaurende Nar- kosen." Verein. westd. Hals. Ohrendrzte zu Kolrv, April, 1912, 21. Med. Klinik, 1912, 1406. Lucas-Championniere : "Diskussionsbem. liber Bromathyl bei Kreis- senden." Bull, de la Soc. de CUr., 1880, 320 ; Virchow-Hirsch, 1880, 1, 454. Lustig: "tJber die Anwendung und Wirkung der Anasthetika und Narkotika bei Kindern," Yerli. d. XXIX. Jahresver. d. zentral. Dents. Zahndrzte, 1890. Vgl. dent. Monats. f. Zahnheilh., 1891, 355. Auch iiber die Diskussion, s. bei v. Ziemacki, loc. cit., 374-376. Magill : "A New and Eapid Method of Anesthesia," N. Y. Med. Rec, 1893, 21; Okt: ZentralU. f. Chir. 1894, 750; Internat. Med. Rec, 1894; Okt: ZentralU. f. Chir., 1895, 658. Malherbe : "De I'anesthesie au bromure d'ethyle dans la position de Eose pour les petites operations pratiquees sur les voies respiratoires su- perieures," Rev. hehd. de Laryngol., d'Etol. et de Rhinol., 1900, Nr. 26. ZentralU. f. Chir., 1901, 662. Mittenzweig: "tJber todliche Nachwirkung der Bromathylnarkose," Zeitschr. f. Med., 1890, 3, 40. Mittenzweig und Stahn: "Experimenteller Beitrag zur Vergiftung durch Bromathyl," Zeitschr. f. Med., 1890, 3, 373. Montgomery: Am. J. of Ohstet., 1885, 561. Eef. bei Haffter, loc. cit., 110. "Bromathyl in der Geburtshilfe." Moses: Vereinig. west. Hals- u. Ohrendrzte zu Koln, Apr., 1912, 21, "Bromathylnarkose der Chlorathylnarkose gleichwertig fiir Tonsil- lotomien," Med. Klinik, 1912, 1685. Miiller, B. : "Tiber Fettmetamorphose in den inneren parenchy- matosen lebenswichtigen Organen nach einfachen und Mischnarkosen," Arch. f. Uin. Chir., 1905, 75, 896. Muller, B. : "tJber die Anwendung des Bromathyls in der Geburt- shilfe," Berl. Uin. Woch., 1883, 673. Napalkow: "Zur Frage der kombinierten Bromathyl-Chloroform- Narkose," Chir., Aug., 1902; Zentralbl. f. Chir., 1903, 263. Norton: "Bromide of Ethyl as an Anesthetic," Brit. Med. J., 1880, 2, 535; "New Forms of Anesthetics," Brit. Med. Assn., 1865. Nun- neley: Brit. Med. J., 1865,^, 192. Osterlen: "Bromathyl," Korrespond. f. Zahndrzte, 1^89. A LIST OF ANESTHETICS 745 Pauschinger : "Bromiithyl/' Milncliener med. Woch., 1887. Nr. 30, 568. Petsch : "Das Bromathyl unci seine Verwendung als Anasthetikum/' Deut. Monats. /. ZalmheWc, 1888, 471. Phillips: "Ethylbromid in Ophthalmic Surgery," Phil. Med. and Surg. Rep., Feb. 5, 1887, 177. Pomeranzew: "Charakteristik des Bromathyls in bczug auf die Gefar seine Anwendung als Anasthetikum," Cliirurgia, Eussisch, 1897, S. 1. ZentralU. f. CUr., 1897, 462. Eabuteau: Compt. rend, de la 8oc. de Biol., 1876, 28, 49; M. Fraenkel: Loc. cit. "Eecherches sur les proprietes physiologiques et la mode de I'administration de I'ether bromhydrique," Compt. rendu, de I'Acad. des Sciences, 1876, 55, 1394; Virchow-Hirsch : Jaliresher., 1876, i, 415 ; Fraenkel : Loc. cit. "Eecherches sur les proprietes physiologiques et la mode d'elimination de I'ether bromhydrique," Gaz. des Hop., 1877, 50. "Eecherches sur les proprietes physiologiques et la mode d'elimina- tion du bromure d'ethyle ; usage de cet ether ; son action sur la germina- tion et la vegetation," Mem. communique a la Soc. de Biol. Gaz. med. de Paris, 1880, 334, 385 et 411; Virchow-Hirsch: Jaliresher., 1880, i, 455. Eegli: "Eperimentelle Beitrage zur Kenntnis der Wirkung des Bromathyls auf Herz und ISTieren," Diss., Berne, 1892. Eeich: "tjber Bromather und kombinierte (sukzessive) Bromather- Chloroform-Karkose," Wiener med.' WocJi., 1893, No. 23 u. 28, 993, 1046, 1090, 1141, 1178 u. 1224. Eein: "tJber die Mischnarkose von Bromathyl und Chloroform," Chirurgie 5, 530; ZentralU. f. CUr., 1900, 638. Eichelot: "Bromathyl-Chloroform-ISrarkose," Bull, de VAcad. de Med., 1902, ^7, 179. Eitter: "478 Bromathylnarkosen," Anlage 30 zu gurlts. Statistik. Verli. f. XXI. Deut. Chirurgenkongr., 1892, Teil ii, 355. "406 Brom- athylnarkosen," Anlage 12 zu Gurlts. Statistik. Verh. d. XXII. Deut. Chirurgenkongr., 1893, Teil ii, 38. "Bericht iiber weitere 335 Brom- athylnarkosen," Anlage 29 der Gurltschen Statistik. Yerh. XXIV. Deut. Chirurgenkongr., 1895, Teil ii, 519. "Bericht liber 1365 Bromathyl- narkosen," Anlage 21 der Gurltschen Statistik. Verh. d. XXIII. Deut. Chirurgenkongr., 1894, Teil ii, 54. Eoberts: "Case of Death Occurring During the Administration of Bromid of Ethyl," Phila. Med. Times, July 17, 1880. ZentralU. f. CUr., 1880, 639. Eobin: "Note sur un nouvel agent anesthesique, I'ether bromhy- drique," Compt. rendu, de VAcad. des Sci., Paris, 1851, 32, 649. Eose: "Diskussion iiber Bromathylnarkose," Gesell. f. Gehurtsh. u. Gyndkol. zu Berlin, 1883 ; ZentralU. f. Gyndkol., 1883, 546. 746 ANESTHESIA Eoth : "tJber Brom-Ather-j^arkose/' Prager med. Woch., 1906, No. 21 ; Z entrain, f. Chir., 1907, 1048. Salzer : "Einige Worte iiber Narkose im Dienste der Zahnheil- kmide," Pest, med.-chir. Presse, 1893, No. 33 ; Zentralbl. f. Chir., 1893, 853. Scliede: "149 Eromiithylnarkosen," Anlage 31 zu Gurlts. Statistik. Verh. d. XXI. Deut. Cliirurgenlongr., 1893, Teil ii, 360. Scheps: "Das Bromathyl und seine Verwendbarkeit bei zahnarztli- chen Operationen," Diss., Breslau, 1887. Schneider : "tJber das Wesen der Narkose im allgemeinen, mit be- sonderer Beriicksichtigung der Bromathernarkose,'^ Deut. Monat. f. Zahnheilk., 1890, 8, 170 u. 217; von Ziemacki: Arch. f. hlin. Chir., 1891, 42, 732. "Das Bromathyl in der zahnarztlichen Praxis," Verh. d. X. Internat. med. Kongr. zu Berlin, 1890, Bd. 5, Abt. 14, 66. Vgl. Deut. Monat. f. Zahnheilk., 1890, Nos. 8-10. Schroeder : "Ein neuer Betaubungsapparat fiir Bromather," Monats. f. Zahnheilk., 1891, 9, 513. Schwartzkoph : "Erfahrungen mit Bromathylnarkosen," Diskus- sionsbemerkung. Deut. Monats. f. Zahnheilk., 1889, 350. Segond: "Sur I'anesthesie combinee avec le bromure d'ethyle et le chloroforme," Bull, et Mem. de la Soc. de Chir. de Paris, 20, 39 ; Zen- tralbl. f. Chir., 1895, 659. Sims : "The Bromid of Ethyl as an Anesthetic," N. Y. Med. Rec, 1880, 361; Virchow-Hirsch : Jahresher., 1880, 50, 454; Vgl. audi Zen- tralbl. f. Chir., 1880, 714; N. Y. Med. J., 1880, 32, 176. Zentralbl. f. Chir., 1880, 714. Sowers : "Ethyl Bromid, or Hydrobromic Ether ; Cases Operated on under Its Influence," Phila. Med. and Sur. Rep., 1880, 93; Virchow- Hirsch : Jahresber., 1880, 454. Sternfeld: "ttber Bromath}^ und seine Verwendung in der arzt- lichen Praxis," Miinch. med. Woch., 1890, No. 1415, 351, 267. Szuman : "Das Bromathyl und die Bromathyl-narkose," Therap. Monats., 1888, 155 u. 226 ; Zentralbl. f. Chir., 1888. "Uber Bromathyl und die Gefahren der Bromathylennarkose," Gaz. Lekarska, 1890, No. 36 ; Zentralbl. f. Chir., 1890, 1024. Terrier: "Sur I'anesthesie combinee par le bromure d'ethyle et le chloroforme," Bull, et Mem. de la Soc. de Chir. de Paris, 20, 400. Zen- tralbl.f. Chir., 1895, 658. Terrier et Peraire: "Manuel de I'anesthesie chirurgicale," Paris, 1894. Terrillon : "Anesthesie locale et generale par le bromure d'ethyle," Compt. rendu, 1880, 91, 1170. Virchow-Hirsch: Jahresbericht, 1880, 1, 454-455; Gaz. med. de Paris, 1880, No. 22; Zentralbl. f. Chir., 1880, 500. "De I'anesthesie generale par le bromure d'ethyle," Bull. Gen do A LIST OF ANESTHETICS 747 therap., 1880, 300; loc. cit., Bull, de la Soc. de Chir., 1880, 316 et 320. ''Diskussion iiber Bromathyl," 8oc. de Chir. de Paris; Bull de Therap., 1881, 337. Thiem : "Diskussionsbemerkung betreffend Bromathyl-narkose," Verh. d. XIX. Deut. Chirurgcnkongr., 1890, Tcil i, 14. Tschunichin : "Bromathyl in der geburtschilflichen Praxis," Wratsch, 1885, No. 30 ; von Ziemacki : Loc. cit., 730. Turnbull: "Advantages and Accidents of Artificial Anesthesia," Phila., 1879. Virchow-Hirsch : Jahresher., 1880, 1, 454. "Artificial Anesthesia, A Manual of Anesthetic Agents, and Their Employment in the Treatment of Disease." Philadelphia, 1891, P. Blakiston's Son & Company. Vajna: "Bromathylmaske," Anlage 18 zu Gurlts. Statistik. Verh. d. XXII. Deut. Chirurgenkongr., 1893, Teil ii, 43. Veit : "Bromathyl bei Kreissenden," Dishussion in der Gesellsch. f. Gehurtsh. u. Gynah. zu Berlin, 1883; Zentralhl. f. Gynak., 1883, 547. Villeneuve : "Sur I'anesthesie combinee par le bromure d'ethyle et le chloroforme," Bull, et Mem. de la Soc. de Chir. de Paris, 20, 418; Zen- tralhl. f. Chir., 1895, 659. Vutzeys: Bull, de I'Acad. roy. de Belgique, 1876; Zit. naeh M. Fraenkel, loc. cit., 9. WalkhofP: "Todesfall dureh Bromather," Monats. f. Zahnheilh., 1891, 9, 517. Wessler : "Skandinavisk Tidskrift for Tandlakara, 1889," Edition 4. von Ziemacki : Loc. cit., 734 (41 Bromathylnarkosen mit durchschnitt- lich 5 g.). Wiedemann : "tJber das Hydrobromathyl als Anasthetikum am Kreissbett," >S'^. Petersburger med. Woch., 1883. Wietland: "Die Narkosen im Easier Kinderspital," Correspondenz- Blatt f. schweizer Arzte, 1894, 564 u. 597. Wilcox : "Bromide of Ethyl as an Anesthetic," Annals of Surg., 1891, No. 4; Zentralhl. f. Chir., 1891, 1000. Willemer: "64 Bromathylnarkosen," Anlage 37 zu Gurlts. Statistik. Yerh. d. XXI. Deut. Chirurgenkongr., 1892, Teil ii, 365. Williams : "Bromide of Ethyl as an Anaesthetic for Short Opera- tions and as a Percursor to the Administration of Ether," Brit. Med. J., 1882, 1, 402. Witzel, A. "tJber den Gebrauch des Schlafgases in der zahnarzt- lichen Praxis" ( Gef ahrlichkeit des Bromathyls: vgl. 10). Deut. Zahii- heilkunde in Vortrdgen, 1889, Nos. 5-6, Hagen i. W., H. Riesel & Co. Witzel, J. : "Bericht iiber 465 Bromathernarkosen," Monats. f. Zahn- heilh., 1891, 9, 421. Witzel, 0. : "Wie sollen wirk Narkotisieren," Miinch. med. Woch., 1902, 1903. 748 ANESTHESIA Wood: "The Physiological Action of Ethyl-Chlorid and Ethyl- Bromid/' Phil. Med. Times, 1880, 370; Virchow-Hirsch : Jahresher., 1880, 1. 455. V. Ziemacki: "Bromathyl in der Chirurgie," Arcli. f. hlin. Gliir., 1891, 'Jk2, 717. Zimmer : "Mahnung ziir Vorsiclit mit Bromather auf Grand zweier nich niiher mitgeteilter Todesfalle in Berlin," Diskussionsbemerkung. Monats. f. Zalinlieilh., 1891, 9, 518. Ethyl Chlorid. — Monochlorethane is well known as an anesthetic (Heyfelder, 1848; Nunneley, 1849; Snow and Eichardson, 1852.) See Chapter VI. See Kelene, Antidolorin, Loco-Dolor, and EtJiylol. Ethyl Chlorid Bengue. — A purified ethyl chlorid. Ethyl Chlorid C. P. — A "chemically pure" ethyl chlorid, for both local and general anesthesia. Ethyl Chlorid Polychlorated. — This mixture of chlorinated ethyl chlorids, principally tri-, tetra-, and penta-chlorethane, is also known as "Wiggers' anesthetic ether" and as "polychlorated hydrochloric ether." Ethyl Ether.— See Chapter V. Ethyl ether (1 ounce) containing camphor (4 drachms) was used as a local anesthetic quite extensively about 1875. Ethyl Ether-Chloroform Mixtures. — On the production of narcosis with a mixture of 1 volume of chloroform and 5 to 6 volumes of ethyl ether, see Kionka: Jalireslurse f. arztl. Forthildung, 1910, No. 8, 3. Ethyl Formate. — Byasson experimented upon the lower animals with formic ether. He supposed that it was decomposed in the blood into alcohol and alkaline formates. Inhalation of its vapor lowered the temperature as much as 3.5° C, caused muscular relaxation and anes- thesia, with some degree of asphyxia. Its effects resembled those pro- duced by chloral hydrate rather than the effects of an ether. Upon the human subject, the use of 6 or 8 grams only caused drowsiness, with- out any other symptom. Ethyl Hydrid.— Eichardson {Sci. Am. Suppl., No. 515, 8228) stated that the physiological action of this gas was generally the same as for amyl hydrid {q. v.) ; and that its anesthetic value was also practically the same, but less manageable, owing to its being a gas. It was Eich- ardson who introduced ethyl hydrid in 1867. Ethyl lodid. — Hydriodic ether (mono-iodoethane) decomposes quite rapidly even in diffused daylight, the light liberating iodin which colors the ether; the decomposition is very slow in the dark, and may be rendered still slower by the addition of a very dilute solution of soda. It may also be kept in contact with a small amount of mercury. Ethyl A LIST OF ANESTHETICS 749 iodid has been considered unsuitable for clinical purposes, owing to its unpleasant taste and its volatility (b. p., -\- 70-75° C). It acts like chloroform, but anesthesia comes on slowly and is more permanent. On the physiological action of ethyl iodid, see Webster: Bio-Chem. J., 1906, 1, 328. Ethyl Nitrate. — Simpson (1848) found that "nitric ether" was a rapid and powerful anesthetic, but the subsequent headaches and dis- agreeable after-effects were of so serious a nature as to condemn it. Fifty or sixty drops were inhaled. Ethly Nitrite. — "Nitrous ether" was tried by the Committee of the British Medical Association, which reported that it produced "great excitement and convulsions, almost immediately followed by cessation of respiration." Ethyl-o-Anisidin Formate. — Found by Goldschmidt {Chem. Ztg., 25, 329) to be a strong local anesthetic. Goldschmidt (Eng. Pat. 9792, 1898) has also claimed the manufacture of compounds of orthoformic ester with o- and p-phenetidin and anisidin, for use as anesthetics. Ethylene Chlorid.— S-Dichlorethane, CH0CI.CH2CI ("dutch liquid" ; elayl chlorid), has been employed as a general anesthetic instead of chloroform, especially in ophthalmic surgery. Its anesthetic action was first studied by Simpson in 1846, Snow in 1848, Clover in 1848, and Eichardson in 1851. The latter {Sci. Am. SuppL, 'No. 515, 8228) regarded it as a good anesthetic, very much like chloroform in its action, although less rapid. He pointed out that the vapor was pleasant to inhale; that the quantity required for complete anesthesia was 2 to 8 fluid drachms; that the required amount of air by vapor was 5 to 10 per cent; that the stages were induced slowly, with a rather long spas- modic period ; and that recovery was slow, with, in rare cases, vomiting. It "deserves more experimental study." Macleve (Chem. News, 4-1, 154) used a mixture of ethylene chlorid and nitrous oxid. Eeichert (Phila. Med. Times, 11, 518) found that ethylene chlorid (?) caused anesthesia with the usual stages, and that, like chloroform, it depressed the heart and steadily lowered arterial pressiire. The ethylene chlorid on the market is a colorless, oily liquid, which possesses a density of 1.265 at -f- 15° C, and a boiling point of -|- 83° C; it has a pleasant odor and sweet taste, but the vapor is irritating; it is soluble in alcohol, ether, chloroform, and slightly soluble in water. It is said to have a similar action to chloroform, and to have found extensive use as a chloroform substitute. See Wallace: Brit. Med. J., 1910, 1288. Ethylene (Monochloro-) Chlorid.— This anesthetic, called also mono- chlorethylene chlorid, monochlorinated dutch liquid, and vinyl tri- chlorid, has been said to be superior to chloroform and ethylene chlor- 750 ANESTHESIA id. The preparation now on the market is prepared from vinyl chlor- id by the action of antimony pentachlorid ; it is a colorless liquid with a pleasant odor, boiling at + 114° C, and having a density of 1.458 at +9° C. Taube (Am. J. Pharm., 1880, 603; 1881, 119) showed the availability of monochlorethylidene and monochlorethylene chlorids as anesthetics. Ethylene Dibromid. — S-Dibromethane (CHoBr.CHaBr) is a color- less, volatile, emulsifiable liquid, possessing a chloroform-like odor. The density of the product on the market is 3.189 at -]- 15° C, and it boils at + 139-131° C. It is miscible in all .proportions with alcohol, but is insoluble in water. Ethylene dibromid is a cardiac poison and its anes- thetic action is slight. Scherbatschetf (Arch. exp. Path. u. Pliarm., 1903, 47) found that ethylene bromid is not a true anesthetic in lower animals. It is probable that some of the evil effects produced in the early use of ethyl hromid (q. v.) were due to the presence of ethylene bromid in the preparations then in use. Ethylidene Chlorid (Chlorinated muriatic ether; a-dichlorethane ; ethidene bichlorid; chloridene; Aran's ether). — This compound is used instead of chloroform for minor operations, producing rapid narcosis of short duration. Ethylidene chlorid was apparently first used by Snow (see "On Anesthetics" p. 33) in 1851. Richardson states (Sci. Am. Supply No. 515, 8338) that "Snow, who introduced this anesthetic, and who was seized with his first fatal attack while writing upon it, told me he estimated its value as equal to chloroform, an estimate which has been sustained by later experience. The anesthetic has, however, more than once proved fatal, apparently from failure of the circulation, al- though in my own experiments with it on lower animals I once restored a rabbit to life by artificial respiration seven minutes after the natural respiration had ceased." Eichardson found the vapor of "ethene di- chlorid" pleasant to breathe; that the quantity required for complete anesthesia was 3 to 8 drachms; and the required charge of air by vapor was from 5 to 10 per cent. Anesthesia was found to be produced rather more rapidly than by chloroform, with the second or spasmodic stage sometimes acute; but recovery was easy, with no important after-efi'ects, and vomiting was a less frequent accompaniment than after chloroform. Binz (Med. Times and Gaz., 1879, 1) produced human anesthesia by means of ethylidene chlorid and thought it increased the force of circulation; but Eeeve ("New Remedies," 1880, 334) found that it lowers arterial pressure, although it does not suddenly paralyze the heart. See, also, Clover: Brit. Med. J., May 39, 1880, 797; and Comm. Rep., idem, Jan. 4, 1879. The ethylidene chlorid on the market is a colorless, oily liquid, pos- sessing the odor and taste of chloroform; it has a density of 1.178 at A LIST OF ANESTHETICS 751 -|- 15° C., and boils at -\- 58-G0° C. That used by Eichardson possessed a density of 1.174 and a boiling point of -|- 64° C. ; it was undoubtedly lacking in purity, and it would be of value to thoroughly study the physiological action of this compound, using the pure preparation. See /Ether Anwstheticus Aranii. Ethylol. — A purified ethyl chlorid of German manufacture. Eucain-A. — "Alpha-eucain" is the hydrochlorid of.benzoyl-n-methyl- tetramethyl-gamma-oxypiperidin carboxylic methyl ester, CigHgyNO^. HCl.HoO. It was also termed eucainae hydrochloras, since eucain-A O.COCeHj COOCH3 CH,, (or alpha-eucain), is properly the base, of which eucain-A, so-called, is the hydrochlorid. The preparation on the market in 1896 formed colorless crystals and was soluble in about 10 parts of water. Its solu- tion was sterilizable by boiling The base eucain-A is constitutionally closely allied to cocain, and, like the latter, is a local anesthetic; it is, however, cheaper than cocain. Gaetono Vinci (Berl. klin. Wocli., 1896, No. 27) found that, in the case of the eye, anesthesia resulted in 2 to 5 minutes after the applica- tion of a 2 per cent water solution, while its influence lasted from 10 to 15 minutes. Its application was said to cause neither mydriasis nor paresis of accommodation — it did not act on the pupil or contract the arterioles — but to produce a slight hyperemia of the mucous membrane. A number of writers have expressed themselves on the properties of eucain-A, namely: Kiesel: Zahndrztl. Rundschau, 1896, No. 196. Wolff : Zahndrztl. Woch., 1896, No. 472. Berger : Rev. de therap. med. chir., 1896, 355. Vollert: Munch, med. Woch., 1896, Nos. 22 and 37. Gorl: Therap. Monatsh., 1896, No. 7, 378. Deneffe: Le Scalpel, Sept. 13, 1896, No. 11. 752 ANESTHESIA Fuller: Internat. J. of Surg., 1896, No. 9. Forster: Langsdale's Lancet, August, 1896. de Mets : Belg. mcd., 1896, No. 43. Legueu: Presse medicale, 1896, No. 88. Vinci: Virchows Archiv, IJ^S, 78; Therap. Monatsh., 1896, 330. Carter:' Pharm. J., 1896, No. 1360. ■ Zwillinger: Pest. med. cliir. Presse, 1896, Nos. 44 and 45. Best: Deut. med. Woch., Sept. 3, 1896, 573. Vogt : Bull. Gen. de Therap., 1897, 112. Bocquillon: J. med., Paris, 1897, No. 37. Eeclus : La France Med., 1897, No. 8. These journal contributors seemed to be favorably impressed with eucain-A on the whole and regarded it as a suitable substitute for cocain, although Vollert, Zwillinger, and Best drew attention to the irritating action, which was so considerable that even a 1 per cent solution caused a sensation of pain and burning. Vollert {loc. dt.), as well as Wiiste- feld {Miinch. med. Wocli., 1896, No. 51), also observed that mydriasis and accommodation were affected, but not in the same degree as by cocain; they also objected to the destructive action on the epithelium of the cornea and conjunctiva. Deneffe noticed that eucain-A hardened the tissue to such an extent as to make it difficult to introduce a suture needle through it. In 1897 there were two varieties of eucain on the market, viz.: Eucain-A and Eucain-B (q. v.). Schmitt ("Nouveaux remedes," 1897, 353) pointed out that eucain-B was superior to eucain-A, inasmuch as it was 3 to 3 times less toxic. Eucain-A was, in 1897, prescribed in the form of an ointment for producing anesthesia on mucous membranes, and in painful wounds, and for itching piles, pruritus ani, and pruritus pudendorum {Therap. Monatsh., 1897, No. 2, 127) ; and the majority of the clinical observations published during this year related to eu- cain-A, while it was ascertained that eucain-B was particularly suitable for ophthalmic operations. For experimental data relating to the physiological action of eucain, as compared with that of cocain, consult the following contributions on the subject: Pouchet: Nouveaux remedes, 1897, 169; J. de med. de Paris, 1897, No. 10. Von Eecke: Belgique med., 1897, No. 790. Charteris : Brit. Med. J., 1897, No. 1891. Noel : Sem. med., 1897, No. 26, 210. Vinci : Virchows Archiv, 1897, No. 2, 145. Schmitt : Nouveaux remedes, 1897, No. 12, 353. Hobday: Brit. Med. J., 1897, No. 1901. Legrand : Nouveaux remedes, 1897, 161. A LIST OF ANESTHETICS 753 On the therapeutic application of eucain-A, see Keclus-IIernette: Nouveaux remedes, 1897, 172. On the employment of eucain-A in surgery, see the following papers : Home: Brit. Med. J., Nov. 27, 1S97. Hernette: T/?,e56!, Paris, 1897. Legrand: Nouveaux remedes, I'^'d^, IQl. Jarrow: Med. Eec, 1897, 49. Legueu and Lihou: Presse med., 1897, No. 15, 80. Lohmann: Therap. Monatsh., 1897, 427. Legueu and Lehuell: Gaz. des Hop., 1897, No. 19, 20. Heinze : Vircliows Arcliiv, 1898, 466. Eeclus: Therap. Woch., 1897, No. 8, 191. Hackenbruch: "Oertliclie Schmerzlosigheit bei Operationen," Wiesbaden, 1897. Spencer: Univ. Med. Mag., Nov., 1896; Med. and Surg. Rep., Nov. 28, 1896. These contributions, together with many others on the bearing of eucain in ophthalmic surgery, rhino-laryngology, and otology, dental surgery, and in the treatment of urethral diseases, showed that eucain-A, or rather the eucains, are endowed with considerable anesthetic power. Eucain-A was objected to, especially by ophthalmic surgeons, particu- larly because it produced a slight irritation on the mucous membrane; and it may be said that it was practically discontinued on the introduc- tion of eucain-B {q. v.). Moreover, eucain-A is more toxic than eu- cain-B in the proportion of about four to one. Eucain-B. — "Beta-eucain," beta-eucain hydrochlorate, 2, 6, 6-tri- methyl-4-benzoxy-piperidin hydrochlorid, or benzoyl-vinyl-diacetone- alkamin hydrochlorid. CH3 -CH NH.HCl CH3 -CHo CH.OcCGCeHe) CH2 CH„ or C5He.C7H50o.CH3.NH(CH3)oHCl, is a white crystalline powder pos- sessing the following solubilities at ordinary temperatures : In wate • 3.5 per cent. In alcohol 3.5 " " In chloroform 15.0 " " In glycerin 2.0 " " 764 ANESTHESIA One part of beta-eucain hydrochloric! is soluble in 5 parts each of anilin and alcohol, and is insoluble in olive oil and paraffin oil alone, or in ethyl ether in material amounts. Suspensions with lanolin and the heavy mineral oils may be prepared by first mixing the salt with 4 to 5 parts of hot water. It fuses with decomposition at -\- 268° C. Benzoyl-vinyl-diacetoue-alkamine was proposed by Vinci as a local anesthetic in 1897; it is an alkaloid related to Tropacocain (q. v.) Vinci termed it eucain-B (beta-eucain), while the earlier preparation, which is decidedly of less value, had been designated eucain-A (g. v.). This nomenclature, as shown by Marcinowski, gave rise to some confu- sion and error; but, since eucain-A is now off the market, this need no longer exist. The free base, the proper eucain-B, is, like cocain and eucain-i^, almost insoluble in water; but it combines with acids to form soluble salts, of which that with hydrochloric acid has been most em- ployed. It is for this reason that beta-eucain hydrochlorid has been commonly referred to as eucain-B or beta-eucain. The preparation has displaced eucain-A, and is employed as a local anesthetic in dentistry and ophthalmic practice, and, like cocain, is mixed with ethyl chlorid for inducing local anesthesia by spraying or plugging. Schmitt (Nouveaux remedes, 1897, 353) stated that eucain-B is superior to eucain-A, since it is 2 to 3 times less poisonous, and it has been pointed out that it is less toxic than eucain-A, in the proportion of one to four (Francis and Fortescue-Brickdale's "The Chemical Basis of Pharmacology," 1908, 307). It has been stated that it is somewhat painful to inject, and that it dilates the blood vessels, and so promotes bleeding — disadvantages which may be overcome by injecting beta- eucain in normal saline at body temperature, or by mixing some adrena- lin solution with the preparation. As mentioned under eucain-A, it was ascertained that eucain-B is par- ticularly adapted for ophthalmic operations in 1897 (see Darier: La Clinique ophthalmol, 1897, 210; Dolganoff: Wratsch, 1896, No. 51; Mayrard: Indian. Med. Gaz., 1897, 44; Silex: Therap. Monatsh., June, 1897; and Sweet: Am. Therap., 1897, No. 8). In 1898 its util- ity had not received general recognition, although a number of physi- cians spoke in its favor, and it was given as an opinion by several recog- nized medical authorities that cocain was a more satisfactory anesthetic. Eeclus (Semaine med., 1898, No. 18, 193), supported by Legrand (Nouveaux remedes, 1898, No. 11, 251) recognized the main disad- vantages of eucain-B, as compared with cocain, in the fact that its anes- thetic action was observed to be a little feebler, and that in consequence of its vasodilatory properties it produced hemorrhages, besides causing pain when injected; and Wohlgemuth (Deut. med. Ztg., 1898, No. 33, 337) pointed out that the view that eucain-B was less toxic than cocain was based upon a delusion. Consequently, many looked upon eucain-B A LIST OF ANESTHETICS 755 as by no means a complete substitute for eoeain, and only regarded tropacocain as such. In the next year, however, we find Bardet, Bolo- gnesi, and Touchard {Nouveaux remedes, 1899, No. 3, 49) employing eucain-B, like cocain, mixed with ethyl chlorid for inducing local anes- thesia by spraying or plugging, although the results of this method were hardly so favorable as those obtained with cocain-ethyl chlorid. In this year Porter (Brit. Med. J., 1899, No. 2010, 84) recorded a case in which the injection of eucain into the prepuce, preparatory to circum- cision, gave rise to an extensive edema of the penis and, ultimately, sup- puration at the site of injection. Experiences of this kind seemed to in- dicate that cocain and eucain were by no means identical in their action, and that they were only partially equivalent. In 1900 Lohmann recommended eucain-B as a substitute for cocain in Schleich's method of infiltration (Therap. Monatsh., 1900, No. 9, 478). In the opinion of Engelmann (Miinch. nied. Woch., 1900, No. 44, 1532), however, eucain-B was not available as a substitute for cocain in Bier's method of cocainizing the spinal cord, since it did not in this re- spect possess any advantage over cocain. In 1901 Gray (Lancet, 1901, No. 4045) published new methods of applying eucain-B ; he employed the compound in combination with co- cain for local anesthesia in the ear, nose, and throat. In opposition to the view of Engelmann, expressed the previous year, Fink (Prager med. Woch., 1901, April 11 and 18) recommended eucanization of the spinal cord by Bier's method in those cases in which cardiac, pulmonary, and renal complications, or the age and feebleness of the patient, precluded the narcosis by chloroform. It was at this time that beta-eucain ace- tate (q. V.) began to be used. More recently eucain-B has been used with successful results in the treatment of sciatica by Lange (Munch, med. Woch., 1904, No. 52), and by Opitz (Klin.-therap. Woch., 1907, No. 14) and Gallatia (Gynakol. Rundschau, 1907, No. 21). H. Braun, in his text-book on local anesthesia, published in Leipzig in 1905, pays many tributes to the properties of eucain-B. He points out that he and Heinze have shown that it is entirely equal in effect to cocain when endermically administered, and that there is no pain or specific irritation from the injection even when 10 per cent solutions, made with the aid of heat, are employed. Even 0.005 per cent solutions effect a distinct diminution of sensibility, and eucain anesthesia is slightly less persistent than cocain anesthesia under like conditions, although a 1.5 per cent beta-eucain solution has about the same effect as a 1 per cent cocain solution in the duration of the anesthesia. No dam- age, we are told, is done to the tissues by the injection of an osmotically indifferent and moderately concentrated beta-eucain solution. Braun also states that the local anesthetic properties of beta-eucain solutions 756 ANESTHESIA are, in general, equal to those of a cocain solution of slightly less con- centration; its diffusive action is somewhat less, but it can be increased by making the solution stronger. Dolbeau, Schmidt, Dumont, and Le- grand found that the fatal dose of beta-eucain was 3 to 3% times greater than that of cocain; Braun's experiments gave similar results for equal concentrations, but he could not agree with Dolbeau when he stated that, on intravenous injection, beta-eucain was as poisonous as cocain. He found that there was an important difference in favor of beta-eucain under these circumstances. Braun stated that the literature contains no records of poisoning by beta-eucain, except in the cases in which it was employed for lumbar anesthesia. He thought, however, that these ill effects after lumbar injection were undoubtedly chiefly due to the actual contact effects of the injected fluid on the central nervous system, and that they were not due at all to absorption phenomena. On eucain-B in infiltration analgesia, see Houghton : J. Roy. Army Med. Corps, April, 1905; Tinker: J. Am. Med. Assn., Feb. 11, 1905; and Parker: Chicago Med. Rec, April 15, 1905. On eucain-B in local anesthesia, see Link: Indiana Med. J., June, 1905; Harrison, Ya., Hosp. Bull, Oct. 15, 1904; Hildebrandt: Berl Jclin. Woch., May 1, 1905; Marquis and Kraft: J. Am. Med. Assn., April 22, 1905; Tuller: Dental Cosmos, April, 1903; Connell: Ann. of Surg., Dec, 1903 ; Witherspoon : Interstate Med. J., July, 1903. The literature relating to eucain-B is quite extensive and cannot be included here in its entirety. Suffice it to say in conclusion that it is recorded as a local anesthetic which has been favorably reported upon in more than one hundred journal contributions; that it is said to pos- sess the same analgesic power as cocain, but is only one-fourth as toxic; that it does not affect the heart or the nervous system, not causing local irritation or general intoxication; that it is devoid of the stimulating powers which render cocain, particularly when used in the nose and throat, so seductive a drug; and that its solutions are permanent and undergo no change when boiled. Dusterbehn (Apoth.-Ztg., 26, 22) found that, when eucain-B is heated at + 100° C. with 10 times as much sulphuric acid, benzoic acid splits off; in the case of eucain-A, however, methyl benzoate is formed. The Deut. Arzne. states the contrary. On reactions for differentiating between alpha and beta-eucain, see Saporetti: Boll. chim. farm., J/S, 479. The deportment of these com- pounds with various reagents is given and discussed, and novocain, nirvanin, alypin, and cocain are also considered. Eucain Acetate. — In 1901 eucain acetate (CigHoiISrOo.CaH.^Oo) was recommended in the place of beta-eucain hydrochlorid, being said to sur- pass the latter as regards solubility. Cohn {Med. Woch., 1901 ; No. 36 ; Therap. Monatsh., 1901, No. 11, A LIST OF ANESTHETICS 757 595) employed eucain acetate in the form of a 2 per cent water solution, and produced, with the application of as little as 4 or 5 drops, complete anesthesia, which set in within 3 minutes and lasted for 10 to 15 min- utes, so as to be available for the extraction of foreign bodies, the gal- vano-cauterization of corneal ulcers and pterygia, and the performance of minor operations on the lacrymal apparatus and the conjunctiva. Eucain acetate therefore appeared to be well adapted for minor opera- tions on the eye — an anesthetic not likely to fail except in cases where portions of the anterior half of the bulbus were per se congested with blood and irritated. Eucain acetate solutions were said to be capable of boiling without danger of decomposition. This salt of eucain is, however, no longer on the market. Eucain Lactate. — Beta-eucain lactate (3, 6, 6-trimethyl-4-benzoxy- piperidin lactate; benzoyl vinyldiacetone-alkalamin lactate) has the fol- lowing composition: CH.O.CO.CcHb HaC ■>c CHs CH, CH.CHs NH.CHo.CH(OH).COOH It is a white crystalline powder, fusing at about -|- 152° C. and pos- sessing the following solubility at the ordinary temperature : In water 22 per cent. In alcohol 11 " " In chloroform 20 " " In glycerin 5 " " The water solution is feebly alkaline to litmus. One part of eucain lactate is said to be soluble in 5 parts each of anilin and alcohol, and it may be dissolved in paraffin oil by the aid of chloroform. It is said to be insoluble in olive oil and paraffin oil alone, and not to be soluble in ethyl ether in material amounts. Suspensions in lanolin and the heavy mineral oils may be prepared by first mixing the salt in 4 or 5 parts of hot water. Beta-eucain lactate is prepared according to the process claimed in U. S. Patent 657,880 of Sept. 11, 1900. It is said to have all the prop- erties of Beta-eucain Hydrochlorid (q. v.), but to possess the advan- tage of being over six times as soluble in water. 758 ANESTHESIA Langgaard {Therap. Monatsh., 1904, No. 8, 416) advocated the em- ployment of eucaiii lactate for local anesthesia, since he found it to be non-irritant, to induce neither hyperemia nor local anemia, and to cause no shrinkage. He stated that it is appropriately applied in the form of the following solutions : In ophthalmic surgery 2 to 3 per cent, solutions. In dental surgery 2 to 3 " " " In anesthesia by infiltration 0. 12 " " " In regionary anesthesia 2 to 5 " " " Surgery of nose, throat and ear 10 to 15 " " " According to Langgaard, solutions of a concentration of less than 1 per cent should have added thereto 0.8 per cent of sodium chlorid, 0.6 per cent of which should be added to 1 to 2 per cent solutions of eucain lactate. Katz (ibid., 1904, No. 8, 419) was the first to treat diseases of the throat, nose, and ear with the aid of this preparation, whereby he obtained very satisfactory results. Braun, in his text-book on local anesthesia referred to above, stated that eucain lactate has the same anesthetic effect as the hydrochlorid, and is equally free from irritative properties. He recommended that it be used instead of beta-eucain when a readily soluble salt of eucain is desired. On the use of eucain lactate in eye, nose, ear, and throat work, see the following : Ellis: Cal. State J. of Med., May, 1905; Harris and Wilson: Laryngoscope, June, 1905; Meyer: Therap. Monatsh., May, 1"905. On its iise in ano-rectal surgery, see Pennington: J. Am. Med. Assn., April 8, 1905; and Am. Med., July 29, 1905. Eucain-snuifpowder. — Lactose with 2 to 3 per cent of eucain hydro- chlorid, also with an addition of 0.01 per cent of adrenalin. Eucalyptus Extract. — This has been used as a local anesthetic in dental operations. Eucapren. — A local anesthetic solution of suprarenalin (1 in 5,000) containing 1 per cent of beta-eucain lactate. Eucarenalin. — An anesthetic consisting of a 1 per cent solution of beta-eucain lactate in 1 to 2,000 of suprarenalin. This preparation was made for the English market, but the name is now discontinued. See Eucapren. Eudont. — Two separate liquids : One a solution of oil of cloves, cam- phor, alcohol, and chloroform; and the other a mixture of tincture of iodin, glycerin, and tincture of opium. Eudont is employed in den- tistry. Eudrenin. — This is a solution of eucain hydrochlorid, intended for dental local anesthesia, the local anesthetic effect of Avhich is said to be augmented and prolonged by the addition of adrenalin chlorid, this lat- A LIST OF ANESTHETICS 759 ter compound having the power of contracting the capillaries and thus preventing the distribution of the eucain hydrochlorid throughout the system. Eudrenin is offered to the trade in 1 c. c. ampules for hypodermic injection, and possesses the following composition: Beta-eucain hydrochlorid . 25 per cent. Adrenalin chlorid 1:10,000. Both compounds are dissolved in physiologic salt solution, 1 c. c. Each ampule therefore contains beta-eucain hydrochlorid, 0.0025 gm. ; adrenalin chlorid, 0.0001 gm. ; and physiologic salt solution, q. s. See Beta-eucain Hydrochlorid. Eugallol. — Ehrmann {Therap. Monatsh., 1910, No. 5, 230) used Eugallol (pyrogallol monacetate) in an aqueous or oily dilution in the treatment of chronic proliferating catarrh, etc., and called the remedy a "caustic anesthetic" or a "caustic mucous membrane anesthetic," in opposition to the anesthesia of purely peripheral neurotic origin pro- duced by cocain, and to the local anesthesia produced by cold. Eugenol (Eugenic acid; carpophyllic acid; para-oxy-meta-methoxy- allyl-benzene). — Used in dentistry as a local anesthetic. An old-fash- ioned remedy for toothache consisted in filling the cavity with a clove, which owes its anesthetic properties to eugenol. Like all the phenols, eugenol acts on nerve endings. Eugenol was recommended by Eed- man (Hollander-Schneidermlihl's "Handbuch der zahnarztl. Heilmit- tellehre," 1890, 149) as an anesthetic suitable for sensitive dentine. It was reported upon by Wittel, Scheuer, and Eichter (J. f. Zalinlieillcunde, 1902, No. 12, 115), and Hertwig (ibid.) praised eugenol as an excellent antiseptic and anesthetic for sensitive dentine and for the pulp. On Eugenol as an anesthetic, see Cohn: Pliarm. Centralh., 40, 33. Eugenol Acetamid. — This compound, CJl3.C3H5.0Cli3.0CH3.C0NH2, is used in the form of a fine powder in the place of cocain as a local anesthetic on mucous surfaces. It forms glossy scales, fusing at -f 110° C. On this preparation, see Cohn : Pliarm. CentraTJi., J^O, 33. Eugenol-alcohol. — On this preparation as a local anesthetic, see Cohn : Pharm. Cenlralli., J^O, 33. Eugenol Esters of the Aminobenzoic Acids. — Eiedel, in German Patent 203,093, of Nov. 7, 1907, claims the substitution for the hereto- fore employed anesthetics, carbolic acid, eugenol, creosote, and other phenol derivatives, of the eugenol esters of the aminobenzoic acids, in the application of arsenic trioxid as a tooth nerve devitalizer. Euphorin. — See Phenyl-uretliane. 760 ANESTHESIA Eupnema (Eupneuma). — This remedy for asthma contains 1 part of anesthesin and 2 parts of subcutin in 100. Euroform Paste. — This dental anodyne and wound packing consists of orthoform 1 dram, europhen II/2 drams, petronol 21/2 drams, and white petrolatum 21/2 drams. Euscopol. — ^A ^'chemically pure, inactive Scopolamin Hydrohromid (q. v.), free from foreign bases." It forms colorless crystals, melting at + 180-181° C, and is soluble in water and alcohol. See Adam: Med. KliniJc, 1911, No. 52, 2026. Eusemin or Eusemine. — A sterile solution in hermetically sealed vials of: Cocain hydroehlorid, 0.0075 gm. (0.116 grain) ; and adrenalin hydrochlorid, 0.00005 gm. (8/1,000 grain), dissolved in physiologic salt solution, 1 c. c. Littaur (Deut. med. Woch., 35, 1277) states that eusemin is a mixture of cocain with adrenalin in physiological salt solu- tion. He considered it of value as a local anesthetic. Gehes Codex (Nov., 1910, 119) states that eusemin is a solution of 0.75 per cent cocain hydrochlorid and 5 per cent of a 1:1,000 adrenalin solution in physiological salt solution. Eiedel's "Mentor" (1911, 153) states that each c. c. contains 0.0075 gm. cocain hydrochlorid and 0.00005 gm. adrenalin hydrochlorid in physiological salt solution. ISTeuhann {Med. Klinih, 8, 780) stated that the toxicity of eusemin was reduced to a minimum on account of its small content of cocain and adrenalin. He reported that it is sterilized in an autoclave. Falkenstein's Zahnpasta. — A paste said to contain an "antiseptic anesthetic." Eilodentol BertagnoUi. — A red-colored alcoholic solution of oils of cinnamon and peppermint, intended for the treatment of odontalgia. Formal. — See MethyJal. Formaldehyd-kelene. — Kelene (q. v.) containing formaldehyd for use in treating hay fever, catarrh, etc. Formanilid. — This compound, phenyl foramid (CgHg.lSrH.CHO), is a reaction product of anilin and formic acid. It occurs in colorless to yellowish crystals, which are soluble in water and alcohol, and which melt at + 46° C. In a paper by Kossa, Tauszk, Preisach, and Meisels {Magyar Orvosi Arch., through Therap. Blatter, 1893, 143), for- manilid is described as a very powerful antipyretic, also acting as an analgesic, producing local anesthesia, even when employed in smaller quantity than cocain. It is said to be used externally in 20 per cent solution to produce local anesthesia in one hour. Formanilid is also said to be hemostatic. Formyl Tribromid. — See Bromoform. Fresenius Anaesthesin-bormelin. — See Ancestliesin-bormelin. Frohmann's Solution. — A dental local anesthetic composed of cocain hydrochlorid, 0.2 part; morphin hydrochlorid, 0.25 part; sodium chlorid A LIST OF ANESTHETICS 761 (sterilized), 0.2 part; antipyrin, % guaiacol, 2 drops; and distilled wa- ter, 100 parts. Gajacyl. — See Guaiacyl. Gasoline. — Used as a local anesthetic in 1879. See Pentdne. Gasu-basu. — See Nervocidin. Glacial. — A mixture of methyl and ethyl chlorids, intended for use as an anesthetic. Gleditschin.— See Stenocarpin. Goldschmidt's Anaesthetics. — According to Goldschmidt {Chem.- Ztg., 26, 743), p-phenetidin and its homologues give with o-formic acid ester, according to the reaction of Claisen, anesthetic compounds of the type of methenyldi-p-phenetidin. Goldschmidt (see Pharm. Ztg., J^6, 323) stated that o-anisidin-ethyl-formate and o-phenetidinethylformate are anesthetics. Gray's Ansestheticum. — Cocain hydrochlorid, 1; anilin, 5; diluted alcohol, 5. For use in ear affections. Grehant's Anesthetic. — A 4 per cent solution of morphin is given, 1/4 c. c. per kilogram of animal, followed in half hour by 10 c. c. per kilogram of a mixture of chloroform 50 c. c. and alcohol and water each 500 c. c. See McNider : Proc. Soc. Exper. Biol and Med., 1913, 10, 95. Guaiacol. — This compound has been used as a local anesthetic; it is said to be innocuous, but irritating. On the production of complete anesthesia by the cataphoresis of a mixture of guaiacol and cocain, see Morton: Dental Cosmos, Jan., 1896; Berten: Berl. Jclin. Woch., 1896, No. 35, 769 ; Marcus : Deut. med. Woch., 1897, No. 10. On the anes- thetic action of Guaiacol, see Cohn: Pharm. Centralh., J/.0, 33. Holland {De7ital Brief, 1901, 8; Odontolog. Blatter, 1902, No. 13, 254) found guaiacol to be a valuable means for the removal of pains in pulpitis, and also a useful addition to arsenic and cocain caustic paste. Hecht {Therap. der Gegenwart, 1909, 354) published a report on the use of guaiacol as an anesthetic and antiphlogistic; this is worthy of careful perusal by every physician, for, although the external use of guaiacol has not met with great favor, this may be largely at- tributed to a certain prejudice founded on the bad effects displayed by excessive amounts. Guaiacol dissolved in olive oil has been employed as a local anes- thetic, although this solution has not met with general favor. It was introduced by Lucas-Championniere. According to Heineck ("General and Local Anaesthesia," 1909, 79), it does not produce anesthesia as rapidly as cocain; it can cause sphacelus; it does not always produce anesthesia; and there is considerable irritation at the periphery of the area of injection. On the employment of guaiacol as a local anesthetic, see thei follow- ing contributions: 762 ANESTHESIA Benoit: "Du gaiacol efc de la cocaine consideres comme anesthe- siques locaux," These de Paris, 1896. Championniere : "Le gaiacol comme anesthesique local et discus- sion," Bull, de VAcad. de Med., July 23, 1895; La France med., 1895, No. 31"; "Emploi du gaiacol pour I'anesthesie locale en reraplacement de la cocaine," Bull, de VAcad. Med., 1895, No. 30; "Emploi du gaiacol pour Tanesthesie locale en remplacement de la cocaine," Lyon med., 1895, ISTo. 33 ; "Anesthesie locale par le gaiacol," J. de Med. et de Chir. Pratiques, 1895, No. 17. Coutant: "Contribution a I'etude des anesthesiques locaux et en particulier du gaiacol en injections intracutanees," These de Bordeaux, 1896. Malot : "Des injections sous-cutanees de gaiacol chloroforme comme analgesique local," These de Paris, 1897. O'Followell : "L'Anesthesie locale par le gaiacol, le carbonate de gaiacol et le gaiacyl," These de Paris, 1897. Eeclus: "Sur la valeur comparee du gaiacol et de la cocaine dans I'anesthesie locale," Bull, de VAcad. de Med., 1896, No. 20. Guaiacol Benzyl Ester. — See Benzcain. Guajacid, or Guaiacyl. — Calcium guaiacol monosulphonate, [(C,H,0,S03),Ca] is a grayish-white powder, freely soluble in water and alcohol, but in- soluble in fatty oils. It acts like guaiacol, as an innocuous local anes- thetic [Andre: J. Pharm. Chim., 1898, (6), 7, i, 324; and Followell: Presse medicale, 1898, No. 25]. Capitain (Beige medicale, 1898, 691) praised guaiacyl on account of its antiseptic and anesthetic properties, as well as on account of its harmlessness. It is said to have been used in minor surgery, dentistry, etc. Guaiasanol (Gujasanol) . — Diethylglycocoll-guaiacol hydrochlorid, CeH,(0CH3).[CH_.N(C2H3),.C00].HCl = Ci3H,9N03HCl, is the hy- drochlorid of diethylglycocoll-guaiacol. It is prepared by the action of chloracetylchlorid on guaiacol and decomposition of the product with diethylamin. It forms small, colorless, prismatic crystals, melting at -f 183° to 184° C. (361.4° to 363.2° F.), having a slight odor of guaiacol and a bitter saline taste. It is soluble in its own weight of water and in 25 parts of alcohol, but is insoluble in ether. The solu- tion in water should be clear, colorless, and give a white precipitate with silver nitrate. The oily base separates on the addition of an alkaline hydroxid. When incinerated on platinum it leaves no residue. It is in- compatible with alkalies and their carbonates. Actions and Uses.— It is antiseptic and anesthetic. It is readily ab- sorbed and splits off guaiacol in the organism with facility. Its anti- septic power is said to be about equivalent to that of boric acid. Guai- asanol has been recommended for the treatment of tuberculosis, both in- A LIST OF ANESTHETICS 763 ternally and subcutaneously. It is also said to be useful as a deodorant and to have given good results in putrid cystitis. Guaiasanol has been tested pharmacologically by Heinz, bacteriologi- cally by Biichner, and clinically by P]inhorn {Munch, med. Woch., 1900, No. 1, 11). Schafer (ibid., 1903, No. 31, 13G3) employed it in the treat- ment of tuberculosis of the larynx as well as of the bones; and Rahn {ibid.^ 1905, 783 and 1806) used the preparation successfully in the treatment of oxyuris vermicularis and for a mouth deodorant. It is said that, when a 1 per cent solution is used for superficial wounds of the eye, there is quite a perceptible anesthetic effect. Dosage. — One to three gm. (15 to 45 grains) in wafers; subcutane- OTisly, 3 to 4 gm. (45 to 60 grains) in 20 per cent aqueous solution; lo- cally it may be used in from 0.1 to 2 per cent solutions. Gujasanol. — See Guaiasanol. Gummitropakokain. — Sterile ampules containing 1.2 c. c. gum solu- tion and 0.05 gm. Tropacocain Hydroclilorid {q. v.). On the employ- ment of this combination in lumbar anesthesia, see Hertel: Munch, med. Woch., 1910, No. 16, 844. Hedonal (Methylpropylcarbinol urethane; pentan-2-ol-urethrane) . — Hedonal is pentan-2-ol-urethane, CH3.CH„.CH,.CH(CH3)O.CO.NH2 = CgH^gOgN. It is a derivative of urethane, differing from ethyl car- bamate, U. S. P., in that the ethyl radicle has been replaced by the radicle of methyl-propylearbinol (pentan-2-ol), CH,.CH,.CH2.CH0H.CH3. It is prepared by heating the secondary methylpropylcarbinol or pentan- 2-ol. CHg.CHo.CHo.CHOH.CH, with urea nitrate under pressure (U. S. Patent No. 659,202), also by other methods (German Patents Nos. 120,863, 120,864, 120,865. It is a white, crystalline powder, hav- ing a faint aromatic odor and taste, melting at -(- 74° C. (165.2° F.), and boiling at -)- 215° C. (419° F.). It dissolves in 120 parts of water at 37° C. (98.6° F.), but is more soluble at higher temperatures, and is readily soluble in alcohol, ether, chloroform, and other organic solvents. It is readily volatilized with the vapors of water or alcohol, and when boiled with alkalies it is split up into its constituents, methyl-propylear- binol, ammonia, and carbon dioxid. On boiling with dilute sodium hydroxid, ammonia is evolved, and may be recognized by the odor and the usual reagents; if then an aque- ous solution of iodin in potassium iodid is added, and the mixture is allowed to cool, the odor of iodoform, derived from the alcohol, is dis- tinctly manifested. It is incompatible with alkalies, their carbonates, and bicarbonates. Actions and Uses. — Hedonal appears to have a greater hypnotic ef- fect than ethyl carbamate. It is said to be followed by no bad after- effects, and to be oxidized in the body to urea and carbon dioxid. It is 764 ANESTHESIA employed in insomnia due to mental overwork, or nervous excitement oc- curring in the course of neurasthenia or hysteria. It is claimed to be a particularly useful preliminary to anesthesia, a hypnotic dose being given, and anesthesia is effected with chloroform after the patient has been asleep for an hour; and recently it has been found to be applicable by itself as an anesthetic for operations, especially if it is applied intra- venously. See Z. fur Chir., 108, 5-6. When hedonal is employed as a preliminary to general anesthesia with chloroform, it must be given at least one hour before the anesthetic, for its absorption is slow. There are said to be objections other than this to its use in this manner. On hedonal as an anesthetic when applied intravenously, see Sichkovski : Russkiy Yrach, 9, 1447 ; Fedoroff : Zen- tralbl. f. Chir., 1910, No. 9; Russisches: J. f. Gehtirtshilfe u. Gynakol., 1910, Nos. 5 and G; Sidorenko: ZentralU. f. Chir., 1910, No. 37. On chloroform-hedonal anesthesia, see especially Krawkoff: Russkiy Wratsch, 1910; Therap. Monaish., 1910, 444. On intravenous hedonal anesthesia, see Sidorenko: Zentr. Chirurg., 1910, No. 37, 1219; Jere- mitsch: Deut. Z. Chir., 1911, 108, Nos. 5-6; Krzizewsky: Russkiy Wratsch, 1911, No. 13; Albinsky: Ibid.; Fedoroff: Therap. Gegen- wart, 1911, 268; Allg. med. Zentralztg., 1911, 305; Zentr. Chir., 1910, No. 19, 675; Lytschkowski : Petershurger med. Woch., 1911, 209. The last five authors confirm the advantages of this method of anesthesia on the whole. For a late report, see Page : Lancet, 182, 1258. Dosage. — One to two gm. (15 to 30 grains), administered dry, fol- lowed by a swallow of water, or in wafers or capsules. Hedonal tablets, 8 grains. Each tablet contains hedonal 0.52 gm. (8 grains). Helleborein. — A glucose from Helleborus niger (Winter Eose; Black Bears Foot), used as a local anesthetic in ophthalmic surgery; on the cornea 3 to 4 drops of a solution containing in 1 drop 0.0005 gm. is said to give complete anesthesia, without irritation, lasting 30 minutes. It is a yelloAvish powder, possessing the composition Cg^HsaOig, and is soluble in water and alcohol. Heufibrol-creme Stauflfer. — This contains Anesthesin (q. v.) and homorenon (ethylamino-acetobrenzcatechin hydrochlorid) . Heufieber-renitol. — Extract of suprarenal gland with a local anes- thetic. Hewitt's C. E. Mixture. — Chloroform, 2 parts by volume ; and ether, 3 parts by volume. Mix. See Hewitt : "Anaesthetics and Their Admin- istration," 3rd ed., 462. Hexahydrophenanthrene. — According to Brissemoret (Compt. rend. 8oc. Biol., 69, 497), this compound has a narcotizing power on such warm-blooded animals as the rabbit. Hexamekol. — This compound of guaiacol with hexamethylene-tetra- A LIST OF ANESTHETICS 765 min is said by Eabow {Chem.-Ztg., 1912, No. 21, 190) to be an anes- thetic. On its employment in practice, see Liidin : Munch, med. Woch., 1911, 48; Chem.-Ztg., Repert., 1911, 554. Hexane. — This hydrocarbon is said to be actively intoxicant, produc- ing a long stage of excitement, followed by deep anesthesia (Francis and Fortescue-Brickdale's "The Chemical Basis of Pharmacology," 1908, 45). It has never been employed as an anesthetic, however. See Octane. Holocain and Adrenalin Ointment. — An ointment said to consist of holocain, 1 per cent; adrenalin chlorid, 4 per cent; hydrous wool fat, 10 per cent; and white petrolatum, 85 per cent. It is put up in collapsible tubes for application to the eye. Holocain Hydrochlorid (Holocainse Hydrochloridum ; Ethenyl- para-diethoxy-diphenyl-amidin Hydrochlorid) . — Holocain hydrochlorid is phenetidy-acetphenetidin hydrochlorid, CH3C( : IST.CBH^.OCgHg) (.NH.C6H,.0C2H5) .HCl = CigH^.N.OoHCl. Phenetidyl-acetphenetidin hydrochlorid is the hydrochlorid of a basic condensation product of para-phenetidin (para-ethoxy-amino-benzene) and acetparaphenetidin (phenacetin). It is prepared by the interaction of molecular propor- tions of para-phenetidin sulphate and acetphenetidin (phenacetin) in the presence of phosphorous oxychlorid, decomposing the resulting holo- cain sulphate with sodium hydroxid, crystallizing the base from alcohol, neutralizing it with hydrochloric acid, and crystallizing. It was first prepared by Tauber (see Centr. f. praht. Augenlieilhunde, 1897, 30). It forms small, colorless crystals, neutral or faintly alkaline, melt- ing at -{- 189° C. (372.2° F.), odorless, faintly bitter, and producing transient numbness on the tongue. It is soluble in 50 parts of water and freely soluble in alcohol. On boiling in ordinary glass vessels, the water solution becomes turbid, owing to a separation of a small quantity of the free base by the alkali derived from the glass. It should form a clear, colorless solution in water, neutral or faintly alkaline, yielding a white precipitate on addition of silver nitrate or of ammonia. The base obtained by precipitation with ammonia and crystallized from alcohol forms colorless needles, which melt at -|- 121° C. (249.8° F.). Incin- erated on platinum, it leaves no weighable residue. It is incompatible with alkalies and their carbonates and the usual alkaloidal reagents. Glass vessels should be avoided in preparing the solution, porcelain being used instead. Only distilled water should be employed. Actions and Uses. — It is a local anesthetic like cocain, but having the advantage of a quicker effect and an antiseptic action. Five minims of a 1 per cent solution, when instilled into the eye, are usually sufficient to cause anesthesia in from 1 to 10 minutes. It is said not to cause the scaliness of the, cornea which sometimes results after the use of cocain. It should never be given internally or be employed hypodermically, for 766 ANESTHESIA it is said to be toxic when so used. In toxic doses it produces general convulsions. Dosage. — It is applied in a 1 per cent water solution prepared in porcelain vessels. The action and mode of application of holocain hydrochlorid, have been discussed in an extensive series of papers; these follow in part. Kuthe : Centr. f. prakt. Augenheilk., Jan., 1897, 55. Jaeuber: Centr. f. prakt. Augenheilk., Jan., 1897, 53. Gutmann: Deut. med. Woch., 1897, No. 11, 165. Deneffe: Sem. med., 1897, No. 15, 114. Berger: Ihid., 1897, No. 31, 25. Lowenstamm: Therap. Monat., 1897, No. 5, 268. Winselmann: Klin. Monat. f. Augenheilk., May, 1897, 150. Hirschfeld: Monat. f. Augenheilk. ,Ms.j, 19,21, Ib'l. Natanson : St. Petersburg, med. Woch., 1897, No. 32, 304. Coosemanns: Presse med., 1897, No. 74, 83. Coosemanns: Rev. held, de Laryng., d'Otol., et de Rhin., Dec. 11, 1897. Chevalier: Bull, de therap., Oct. 23, 1897; Nouveau remedes, 1897, No. 20, 609. Lagrange and Crosse: Bull, med., 1897, No. 104, 1209. Lagrange and Crosse : Bull, med., Feb. 8, 1898. Gires : These de Paris, 1897. Heinz: Centr. f. prakt. Augenheilk., March, 1897. Heinz and Schlosser: Klin. Monats. f. Augenheilk., April, 1897, 114. Carter: Lancet, May, 1897, 1466. Derby : Boston Med. and Surg. J., June 3, 1897 ; and Boston Med. and Surg. J., Jan., 1890. Wood: Ann. of Ophthalmology, Oct., 1897. Holtz: J. Am. Med. Assn., Nov. 13, 1897. Masselon: Arch. d'Ophthalm., Oct., 1897. Wurdemann: Clinique ophthalm., 1898, No. 5. Eandolphe-Westcott-Hotz : Woch. f. Therap. u. Hygiene des Auges, 1898, No. 47. De Landsheere: Clinique ophthalm., 1898, No. 16, 191. Snegirew: Med. Oboshrenie, SO, No. 4. Frassi: Clinica Moderna, 1898, 29. Wurdemann and Black : Ophthal. Rec, Oct., 1897, and Jan., 1898. Hinshelwood: Brit. Med. J., Sept. 3, 1898; Glasgow Med. J., June, 1904. Cheatham: Am. Pract. and News, Aug. 15, 1898. Ellett: Phil. Med. J., Nov. 26, 1898. Randolph: J. Am. Med. Assn., Sept., 1898. A LIST OF ANESTHETICS 767 Trousseau: La Presse med., Apr., 1898, No. 37. Hinshelwood: Klin.-therap. Woch., Sept., 1898, No. 39. Serin i : Archives d'OphAlial., Jan., 1899. Knapp: Archives of OphUial., May, 1899. Guttmann : N. Y. med. Monats., Nov. 3, 1899. Norris: Ophthal. Rec, June, 1899. Schultz : Archiv f. Augenheilh., 1899, J^O, No. 2, 125. Jackson: Col. Med. J., Dec., 1899. Pyle: West. Med. Rev., Jan. 15, 1900. Hale : Chicago Med. Rec, Feb., 1900. Deane: Pac. Med. J., June, 1900. Ellenbogen : Rev. therap. med.-chir., Dec. 1, 1900. Holber Mygind: "Krankheiten cler oberen Luftwege" (Verlag Os- car Coblentz, Berlin), 1901. Brandt: Zahndrztlich Rundschau, 1901, Nos. 468 and 469. Heineck: The Bacillus, Jan., 1901. Zirn: Zentralh. f. praht. Augenheilh., May, 1901. Coulter: Ann. of Otol., Rhinol. and Laryng., Feb., 1901. De Schweinitz : Therap. Gaz., June 15, 1901. Calhoun: Ophthal. Rec, Jan., 1902. Knipp: J. Am. Med. Assn., Aug. 9, 1902. Briggs: Occidental Med. Times, Aug., 1902. Oliver: A?i/i. of Ophthal, Oct., 1903. Bock: "Das erste Jahrzebnt der Abteilung fiir Augenkrauke in Laibach," Wien, 1902; Allgemeine Wiener medicinische Zeitung, 1908, No. 36. Wainwright: The Am. Therap., 1904, No. 1. Church: Ophthalmology, July, 1905. Hydramyl (Amyl Hydrid; Pentylene). — Obtained as a fraction in the distillation of petroleum and proposed as an anesthetic. See Amyl Hydrid. Hydramyl Ether. — A local anesthetic containing equal parts of hy- dramyl and ether. Hydramyle. — To quote Eichardson (Sci. Am. Suppl., No. 516, 8240) : "A mixture made by adding amyl hydrid to zinc in making methylene bichlorid from chloroform. A colorless ethereal fluid. Sp. gr., 0.720. Vapor ethereal, sweet, and very pleasant to breathe; quan- tity required to produce anesthesia, 2 to 4 fluid drachms. Action ex- tremely rapid, complete insensibility sometimes occurring within the minute. Peculiar in its effect in that insensibility from it intensifies for a few seconds after it is withdrawn. Eecovery, when it commences, al- most immediate. An excellent anesthetic for short operations like ex- traction of a tooth. Was administered by author forty-six times to the human subject, with production of insensibility within an average of 768 ANESTHESIA fifty seconds, and without vomiting or any other untoward symptom." Eiehardson introduced hydraniyle in 1871. Hydriodic Ether. — See Etliyl lodicl. Hydrobromic Ether. — See Ethijl Bromid. Hydrochloric Ether. — See Ethyl Chlorid. Hyoscin (or Hyoscine) Hydrobromid. — See Scopolamin Hydro- hromid. Hyoscin, Morphin, and Cactin. — On the use of this combination as an anesthetic, see Lee: J. Minn. Med. Assn., 28, 98. Hyoscin-morphin Mixture. — This anesthetic has been used in ob- stetrical medicine in a dose of 1/100 gr. of hyoscin hydrobromid and 1/4 gr. of morphin sulphate. See Practitioner, July, 1911. Ice and Salt. — Lemke used ice and salt to anesthetize the site of the insertion of the cannula, previous to injecting nitrogen in tubercu- lar pulmonary cavities (Heineck, "General and Local Anaesthesia," 1900, 87). A mixture of salt and snow was highly recommended by Arnott as a local anesthetic, but such a method is troublesome. Ichnol. — An alcoholic solution of ethereal oils (eugenol, etc.) col- ored green by means of chlorophyll. Used in odontolgia. See Jehnol. Idin. — Apparently spirits of camphor. Used in odontalgia. Ac- cording to Eiedel's "Mentor" (1912, 173), a solution of camphor and menthol, or oil of peppermint, in alcohol. Injection Hirsch. — This is said to be a stable solution containing one per cent of mercury oxycyanid and one half of one per cent of Acoin (q. v.), used as a local anesthetic. Iodoform. — Iodoform is said to resemble the other kindred anes- thetics in its physiological action ; in the lower animals it produces mus- cular rigidity, anesthesia, sleep, muscular relaxation, and, in sufficient doses, death. It has not received any real consideration as an anes- thetic for operations. Iso-amylene-beta-pental. — This compound has been used for effecting total anesthesia. Isobutyl Ester of Para-amidobenzoic Acid. — See Cydoform. Isopon. — This preparation contains the alkaloids of opium. See Pantopon. Isopral. — Isopral (triehlorisopropylalcohol), CCI3.CHOH.CH3, is obtained in prismatic crystals, possessing a camphoraceous odor and pungent taste. It has a melting point of -f- 49° C. It is soluble in about 30 parts of cold water, more readily in alcohol and ether. Isopral is a hypnotic, the uses of which are, in general, those of chloral hydrate. The dose is 0.3 to 1.3 gm. (5 to 20 grains). Mertens {Arch. Jclin. Chir., 95, No. 3) found isopral to be useful as a preliminary to chloroform anesthesia when given in the form of rectal injections. Burkhardt {Munch, med. Woch., 1911, No. 15) employed isopral intravenously as A LIST OF ANESTHETICS 7G9 an anesthetic, finding it to possess several advantages over Tledonal (q. v.). Intravenous ether anesthesia seems to liave special advantages when combined with isopral (Burkhardt: Miinch. rned. Woch., 1911, 778). Jehnol. — A solution containing ethereal oils and camphor, colored green with chlorophyll. Used in odontalgia. Johimbin. — See Yohimhin. Kandol. — See Canadol. Katharin. — See Carbon TetracJdorid. Kelen or Kelene. — A purified ethyl chlorid, supplied in a special form of container. There are also preparations of cocaiji and kelene, formaldehyd and kelene, and of the latter with menthol. Kelene-methyl. — A mixture of ethyl chlorid with methyl chlorid for use as an anesthetic. See Z. angew. Cliem., 1901, 261. Keroselene. — A mixture of hydrocarbons from coal oil, possessing a boiling point of -(- 90° F. ; it was jjroposed as an agent for producing anesthesia by inhalation (see Bigelow: Boston Med. and Surg. J., July 11, 1861), but it produced in every case disagreeable and alarming symptoms, as irritation of the air passages, lividity of the surface, mus- cular disturbance, and intermission of the pulse. Koenig's ^ther Anaestheticus. — See zEtlier Ancestheticus (Koenig). Lamellae Cocainae. — Each lamella contains 1/50 gr. cocain hydro- chlorid. Laudanon. — This is an opium preparation containing a combination of difterent opium alkaloids. See Pantopon. On laudanon, see Faust: Miinch. med. ^Yocll., 1912, 2189. Letargin. — In each c. c. are 0.5 gm. extract hamamelis, 0.015 gm. novocain, 0.0092 gm. sodium chlorid, 0.0002 gm. thymol, 0.5 gm. distilled water, and 1 drop of a 1 : 1000 suprarenin hydrochlorid solution; it is used as a local anesthetic in the extraction of teeth and in other minor operations. Letheon. — Morton and Jackson sought to patent their anesthetic under this name. It was soon recognized as ethyl ether (see Chapter I, p. 16). It has been stated that ethyl ether mixed with aromatic oils was termed "Letheon" in 1846. Linhart's A. C. Mixture. — According to Buxton ("Anaesthetics," 4th ed., 288), "Linhart's Mixture" is composed of alcohol, 1 part, and chloroform, 4 parts. Buxton further states {ibid., 294) that it con- tains 20 per cent alcohol — more than is necessary — and gives less good results than the 10 per cent mixture. See also Dumont's "Allgemeine u. lokale Anaesthesie," 117. Linhart's C. E. Mixture. — A mixture of chloroform, 1 part, and ethyl ether, 4 parts. "This mixture is devoid of any danger" (Miiller: "Narkologie," 1908, 492). 770 ANESTHESIA Liquor Ansestheticus. — A very variable mixture obtained by chlori- nating ethyl chlorid. Liquor Hollandicus. — See Ethylene Clilorid. Locasemin. — A local anesthetic, similar to Eusemin (q. v.). Loco-dolor. — A purified ethyl chlorid. London Medical and Chirurgical Society Mixtures. — A — Alcohol, 1 part; chloroform, 2 parts; ether, 3 parts. B — Chloroform, 1 part; ether, 4 parts. C — Chloroform, 1 part; ether, 2 parts. It was found that mixture B was very isimilar in physiological action to ethyl ether (see Med. Chir. Trans., Jfl, 1864) ; that the mixtures A and C were very similar to each other in their action; that A and C exercised a much less depressing effect upon the action of the heart than chloroform alone; that a mixture of ether and chloroform (such as A and C) was as effective as pure chloroform, and a safer agent where deep and pro- longed anesthesia was to be induced. In the opinion of the committee, preference was to be given to mixture A. Ellis ("Anaesthesia with Mixed Vapor," London, 1866) found that, when the mixture A was evaporated, during the six or seven minutes required for the evaporation of half a drachm (two grams) of the liquid, the vapor of ether, almost exclusively, was given off during the first minute, the vapor of chloro- form predominated during the next three minutes, and the evaporation of alcohol occupied the last three minutes. On death from the inhalation of a mixture of chloroform and alco- hol, see Hammond: Am. J. Med. Sci., July, 1858, 41; and on death from inhaling a mixture of chloroform, ether, and alcohol, see Morton and Hewson: Ibid., Oct., 1876, 415. See A. C. E. Mixture; Ancesihol (W. Meyer) ; and ''M. S." Lycoperdon Proteus. — See Puff-ball. Magnesium Salts.— In 1906 S. J. Meltzer {Berl. Jclin. Woch., 1906, No. 3, 73) conducted experiments with the subcutaneous, intravenous, and intraspinal injection of magnesium sulphate. Meltzer reasoned from the fact that intracerebral injections of magnesium salts produced, not convulsions, but evidences of paralysis. The results of his experi- ments, which proved that magnesium sulphate has not an inconsidera- ble anesthetic action, decided Meltzer to employ lumbar anesthesia by means of magnesium sulphate in a number of operations on patients, partly by itself and in part in combination with the inhalation of chlo- roform. He injected 1 c. c. of a 25 per cent sterile solution of mag- nesium sulphate for each 12 kg. of body weight, and found that after 3 or 4 hours there appeared paralysis of the legs and the region of the pelvis, thus permitting of the painless performance of an operation in these regions. Meltzer observed, as secondary actions, undue prolonga- tion of the paralysis and retention of the urine, but reported that these could be avoided by washing out the spinal canal with normal saline A LIST OF ANESTHETICS 771 solution. The heart and blood pressure were said to be unaffected, but the influence on the respiration required careful notice. Desguin (Deut. Med.-Zig., 1907, No. 99, 1102) reported on the innocuous nature of magnesium sulphate as leading to its adoption in the place of the customary anesthetics in certain cases; and Tucker {Therap. Gaz., 1907, No. 5; Revista espec. medicas, 1907, No. 199, 475; Merck's Archives, 1907, No. 6, 178) applied solutions of mag- nesium sulphate as local anesthetics. Delhaye {Presse med., 1908, 397) studied the anesthetic action of magnesium salts from a pharmacological standpoint. He regarded these salts as strong nerve sedatives, able to produce complete anesthe- sia and even paralysis. They have, according to Delhaye, no toxic ac- tion on the heart, although he considered them dangerous to respiration and to the kidneys, and that they should not be employed for producing anesthesia for these reasons. Netter (J. de Med. inter., 1909, 38) and Griffon and Lian {These de Paris, 1908) noted the anesthetic power of solutions of magnesium sulphate, particularly on subcutaneous or intra- venous application. Henderson (J. Pharmacol, and Exper. Therap., 1909, 1, 199) investigated the production of anesthesia by intracerebral injection of magnesium chlorid. More recently the use of magnesium sulphate as an anesthetic has been described by Corrado : II PolicUnico, 1910, 124; but especially Rev. de Therap., 1910, No. 16, 556; Phillips: Klin.-therap Woch., 1910, No. 10, 263; Johnson: Brit. Med. J., 1910, No. 2590, 457; Paterson: Lancet, 1910, No. 4518, 922; and Canestro: Klin.-therap. Woch., 1910, No. 19, 455. Canestro found that the spinal anesthesia produced by magnesium sulphate caused no changes in the central nervous system such as had been observed to follow the use of other anesthetics. Hyndham and Mitchener (J. Am. Med. Assn., July 23, 1910) proved that magnesium sulphate injections paralyzed only the sensory cells and not the motor cells of the cerebral centers. The value of magnesium sulphate in the treatment of tetanus is apparently well established; it depends upon the sedative action of the salt, which persists long enough to enable the brain to render the tetanus poison harmless. Guthrie and Ryan, in a paper on the reported specific anesthetic property of magnesium salts {Am. J. Physiol., 26, 329), claim that the specific anesthetic properties cannot be ascribed to magnesium salts, despite the assertions of Meltzer and others to the contrary. Wiki {Arch, intern. Pharmacodyn., 21, 415) studied the local anes- thetizing action of magnesium sulphate. He was able to confirm the local anesthetizing effect and to show that the action is augmented with the concentration of the solution. Meltzer has more recently injected magnesium sulphate (1 c. c. of a 25 per cent solution in sterile water per kg. of animal) into the femoral 772 ANESTHESIA muscle, and thereby obtained great relaxation with much smaller amounts of ether. The animal is first anesthetized with ether by the cone method, and the solution injected, the infiltrated muscle being im- mediately massaged thoroughly. By giving calcium salts Just before the ether is discontinued, the subject is brought quickly from under the in- fluence of the magnesium. Maier's Radikal-anasthetikum. — See Radilcal-andstlietihum Maier. Mannin. — Amido-oxybenzoic acid methyl ester, a local anesthetic. Martindale's Mixture. — A volumetric mixture, the ingredients of which are said to evaporate almost uniformly. It is composed of ab- solute alcohol (0.795), 1 volume; chloroform (1.497), 3 volumes; and ethyl ether (0.720), 3 volumes. See A. C. E. Mixture, from which Mar- tindale's mixture differs only in the specific gravity of the ingredients and from the fact that "the three ingredients are intended to evaporate uniformly." There is said to be no advantage in this mixture over the A. C. E. mixture, and, since the specific gravities mentioned in either differ from those for the corresponding anesthetics used in the United States, the A. C. E. mixture may be defined as alcohol, 1 part; chloro- form, 3 parts ; and ether, 3 parts ; the best quality of ingredients to be employed and the mixture freshly prepared. On Martindale's mixture, see "The Extra Pharmacopoeia," by Mar- tindale and Westcott, 12th ed., 235; and Hewitt's "Anaesthetics and Their Administration," 3rd ed., 467. Med. Chir. Soc. of London's Mixture. See A. C. E. Mixture, and London Medical and Chirurgical Society Mixtures. Menthol Thymate. — Used in odontalgia. Menthophenol. — An aromatic liquid, soluble in alcohol, ether, and chloroform, but not in water or glycerin, obtained by fusing 3 parts of menthol with 1 part of phenol; it possesses antiseptic and analgesic properties. Menthophenol Cocain. — A local anesthetic, obtained by fusing equal parts of menthol, crystalline phenol, and cocain hydrochlorid, also known as Bonaine (q. v.). Von Mering's Mixture. — A mixture of chloroform, 1 part, and di- methylacetal, 2 parts (Dumont: "Allgemeine u. lokale Ana^sthesie," 117). See DimethyJacetal. Metsethyl. — This mixture of ethyl and methyl chlorids is mentioned in Z. angctr. Cliem., 1901, 2G1. See Methethyl Methaform. — Methaform, known also as acetone-chloroform, chlor- butanol, and dimethylcarbinol chloroform, is a white, crystalline com- pound possessing a camphor-like taste and odor. It occurs in delicate needle-like crystals, sparingly soluble in water, but quite soluble in chloroform, alcohol, ethyl ether, and glacial acetic acid. Water, at the ordinary room temperature, dissolves about 1 part in 100. Methaform A LIST OF ANESTHETICS 773 is not decomposed by acids or alkalies. It melts at + 9G° to 97° C, boils at + 167° C, and sublimes at body temperature in characteristic crystals. Methaform is hypnotic, analgesic, anesthetic, and antiseptic. In physiological action it closely resembles chloral hydrate, ])ut is said to be less likely to irritate the stomach and to exert a less depressant ac- tion on the circulation. In addition, it is said to paralyze the sensory nerve terminals when applied locally, and hence, like cocain, to be ap- plicable for local anesthesia, especially in infiltration anesthesia. In experimental work upon the lower animals, where anesthesia is desired, it is said that methaform is almost an ideal anesthetic when adminis- tered in doses of 2 to 5 grains per pound weight of the animal. Cocain hydrochlorid solution with methaform (3 per cent and 4 per cent cocain) is offered in 1 ounce vials. It is said that methaform, being strongly antiseptic as well as a local anesthetic, is perhaps the best preservative for cocain solutions. It is reported to not only pre- vent decomposition of the cocain, thus rendering the solution stable, but to be a material aid in the production of. anesthesia. It is furthermore said to be of value in preventing infection of the tissues by the hypo- dermic needle employed to introduce the cocain solution. Cocain solu- tions with methaform are said to be of value in flental and other minor surgical operations. See CMoretone. Methane. — T. Nunneley, in 1849, and Richardson, in 18G7, intro- duced methane as an anesthetic. Eichardson found it to be "a very good anesthetic, but not practical, owing to ics being a gas" (Sci. Am. Suppl., ISTo. 51G, 8240). He found that it could be breathed without irritation; that the quantity required in air for anesthesia was 35 per cent; and that the anesthesia was slowly induced without any active spasmodic stage. Methenyl-o-Anisidin. — According to Goldschmidt (Cheni. Ztg., 25, 329), this compound possesses anesthetic properties; its guaiacol sul- phonic acid salt also has an anesthetic action. Methenyl-p-Phenetidin. — A local anesthetic. Methethyl. — A mixture of ethyl and methyl chlorids, used as a spray for producing local anesthesia. Methoxycaffein. — This compound [CgH9(0CH3)I^^0o] is a white bulky powder, melting at -|- 177° C, and slightly soluble in water, more readily soluble in dilute ak'ohol. It is used subcutaneously as a local anesthetic (1 c. c. of a 2 per cent solution). Methyl Acetylsalicylate. — Pototzky (Arch, de Pliarmacodyn., 12, 132) found this ester to possess local anesthetic properties. Methyl Alcohol. — B. W. Richardson introduced methyl alcohol as an anesthetic in 1867. He found that the vapor was pungent to breathe and slightly provocative of coughing. The quantity of liquid required 774 ANESTHESIA for complete anesthesia was from li/o to 2 ounces by volume, and the required charge of air was to saturation. The action was very slow, and with distinct symptoms of alcoholic intoxication; a full hour was required to produce insensibility, which at the deepest was insuthcient to destroy reflex irritability. The breathing was stertorous, often with bronchial rales; the recovery was very slow, being four to six hours in deep anesthesia; and the temperature was reduced 3° F. Eichiardson regarded methyl alcohol as an indifferent anesthetic, owing to the length of administration and slow recovery, but considered the danger prac- tically nil. He learned that when the inhalation was enforced to the production of death, the circulation and respiration ceased simultane- ously (Sci. Am. Suppl., No. 516, 8240). The use of methyl alcohol as an anesthetic is highly objectionable. Methyl alcohol is less poisonous to lower plants and infusoria than ethyl alcohol, but for higher animals, and especially for man, it is a severe toxic agent. It occasions toxic effects whether it is taken internally or inhaled through the lungs. Methyl alcohol is treated fully by Basker- ville in his report to the State Factory Investigating Commission of New York, 1913, which should be consulted. Methyl Bromid. — B. W. Eichardson introduced this compound as an anesthetic in 1867. He found the physiological properties to be an- alogous to those of Ethyl Bromid (q. v.), but causing more irritation, with salivation. The anesthetic value was stated by Eichardson {Sci. Am. Suppl., No. 516, 8240) to be analogous to that of ethyl bromid, but less practical, owing to the extreme volatility and lesser steadiness of action. Methyl bromid is only slightly toxic. Methyl Chlorid (Methyl Chloridum).— Methyl chlorid (CH3CI) is the hydrochloric acid ester of methyl alcohol. It occurs, in the com- pressed state, as a colorless liquid, having an ethereal odor and a sweet taste. Methyl chlorid is insoluble in water, more readily in alcohol, freely in ether and chloroform, and also in acetic acid. It should be neutral to litmus paper. At about — 25° C. ( — 13° F.), it has a specific gravity of 0.991, and boils at about — 21° C. ( — 5.8° F.). It burns in the air with a greenish flame, though it is not highly inflammable. The neutral solution is not precipitated by a solution of silver nitrate, nor is there any reaction with potassium iodid and starch paste. If the liquid is allowed to evaporate it is a powerful refrigerating agent. At very low temperatures it forms with water a hydrate, CH3CI.9H2O. It should not react alkaline to litmus (absence of ammonia and methylated ammonia — methylamin). It should not immediately form a precipitate with sil- ver nitrate. On evaporating it should leave no residue and emit no odor of methylamin. Action and Uses. — By its evaporation a temperature of — 23° C. A LIST OF ANESTHETICS 775 ( — 9.4° F.) is produced, while if the evaporation is accelerated by means of a current of air a temperature of — 55° C. ( — 67° F.) may easily be reached. On account of this property, it is used as a local an- esthetic in the form of a spray, but its use requires caution, since it is apt to produce blisters. The diluted vapor is said to be non-poisonous. Methyl chlorid is said to be an efficient general anesthetic, which has practically no influence on the circulation, but fails to produce com- plete muscular relaxation. It is used as a general anesthetic, mixed with ethyl chlorid and ethyl bromid. Eichardson introduced it as a general anesthetic in 1867. He found the gas very pleasant to breathe, and determined the required charge of air to be 15 per cent. The an- esthetic action was found to be rapid and most effective, with the brief- est spasmodic stage or with no such stage at all; insensibility was deep, and recovery was rapid, not being longer than five minutes from the deepest narcotism, and with no bad after-effects. Vomiting was rare. Eichardson (Sci. Am. Suppl., No. 516, 8240) considered it one of the best and safest of anesthetics — the safest of all anesthetics containing chlorin, but difficult of management, owing to it being a gas. When carried to the point of death, the heart was found to outlive the respira- tion, and the muscles to retain their irritability after death for periods of three to four hours. The heart pulsated spontaneously, in the case of a rabbit killed by the vapor, for forty minutes. Methyl Chlorid is less toxic than Methylene Chlorid (q. v.). Eichet and Marcille (Sem. med., 1902) reported that methyl chlorid acted on the animal as an efficient anesthetic and that it had practically no influence on the circulation. Dosage. — When sprayed on tLe skin, the part should be partly pro- tected by a thin layer of cotton wool. When used locally, cotton wool soaked in liquid methyl chlorid may be applied to the skin over the painful area, but care should be taken that blisters are not formed. In order to avoid this, a mixture with ethyl chlorid has been recommended. Methyl Chlorid-Alcohol. — The Committee of the British Medical Association {Brit. Med. J., Jan. 4, 1879) reported that methyl chlorid, liberated from its alcoholic solution, was not very potent. A rabbit was subjected to its inhalation, but ^^after somewhat prolonged use there was not any abolition of reflex action, and the animal almost immedi- ately recovered. The only effect was slight drowsiness." Methyl Chlorid-Ether. — Hermann and Eichardson found the solu- tion of methyl chlorid in ether to be a very efficient and agreeable an- esthetic. Methyl Chloroform. — See Trichlorethane. Methyl Cinnamenylacrylate. — Pototzky (Arch, de Pharmacodyn., 12, 132) found that this ester had local anesthetic properties. Methyl Dichlorid (Methyl Bichlorid, Eichardson-Merck) . — A mix- 776 ANESTHESIA ture of 1 volume of methyl alcohol and 4 volumes of chloroform for anesthesia by inhalation. Not to be confounded with Methylene Bichlorid. Methyl Ether (Dimethyl Ether; Methyl Oxid).— This anesthetic gas has been sold in ethereal solution, but is not used in the United States. It was introduced by Eichardson as an anesthetic in 1867. He found the gas pleasant to breathe, causing no irritability. The required charge of air was 25 per cent. The anesthetic action was rapid up to complete insensibility, without any manifestation of a spasmodic stage; in fact, Eichardson found that methyl ether possessed the remarkable property of destroying sensibility before destroying consciousness. The recovery from deep anesthesia was rapid, and was unattended by any bad symptom or vomiting. TJie temperature was reduced 1° to 2° F. in deep anesthesia. To quote Eichardson {Sci. Am. Suppl., No. 516, 8240) : "I consider methylic ether to be the safest of all anesthetics hitherto discovered. Pigeons and rabbits will remain anesthetized in a full anesthetic atmosphere for twelve minutes without dying, and after being allowed to die are recoverable by artificial respiration seven min- utes after cessation of all signs of life. The one practical objection to methylic ether as an anesthetic consists in it being a permanent gas at ordinary temperatures. I have administered it successfully twenty-seven times to the human subject." According to Francis and Fortescue-Brickdale ("The Chemical Basis of Pharmacology," 1908, 104), methyl ether acts very like nitrous oxid, producing a rapid and transient anesthesia. The same authors call attention to the fact that it would be interesting to ascertain whether methyl-ethyl ether (CFIo.O.OoHg) has any advantages over ordinary ethyl ether. On the properties of methyl ether, see J. Pharin. Cliim. (4), 19, 438. Methyl Fluorid. — Moissan stated that methyl fluorid possessed an- esthetic properties {Bull, de I' Acad, de Med. de Pmis, 1890). Methyl Hydrate or Hydroxid. — See Methyl Alcohol. Methyl lodid. — This compound was experimented with by Eichard- son and Simpson, who found that its vapor could be respired, even to the induction of anesthesia. Simpson regarded it as powerful but dan- gerous. It has also been employed as a local anesthetic. Methylal (Methylene-dimethyl Ester; Formal; Methylene Dimethy- late). — This compound [CHo(0CH3)2], prepared by distilling together methyl alcohol, water, sulphuric acid, and manganese dioxid, is a color- less volatile liquid with a chloroform-like odor and a pungent taste; it possesses a density of 0.855 at -\- 15° C, and boils at -|- 42° C; it is easily soluble in water, alcohol, and oils. At the present time it is said to be used as a 10 per cent liniment or ointment as a local anesthetic. Eichardson introduced methylal as an anesthetic in 1868. He found A LIST OF ANESTHETICS 777 that its anesthetic value was the same as that of Methyl Alcohol (q. v.) ; that its vapor was agreeable to breathe, and that the quantity required to produce anesthesia was from 1 to 3 fluid ounces, the required charge of vapor in air being 35 per cent. "Kecovery very prolonged, but with- out painful symptoms or vomiting" (Sci. Am. Suppl., No. 516, 8240). According to Francis and Fortescue-Brickdale ("The Chemical Basis of Pharmacology," 1908, 104), methylal produces anesthesia slowly; the action is prolonged and deep, but somewhat uncertain; and patients quickly become accustomed to it. "Methylene." — ^A mixture of methyl alcohol, 30 per cent (1 vol- ume) ; and chloroform, 70 per cent (4 volumes), proposed by Eegnault and Villejean. It is said to be inferior to and less safe than alcohol- chloroform mixture, 1:10, and is seldom used at the present time. "Methylene Bichlorid." — See Narcotil. Methylene Chlorid (Methylene Bichlorid; Dichloromethane ; Meth- ene Chlorid). — This compound (CH2CI2) is prepared by the action of zinc and hydrochloric acid on a mixture of alcohol and chloroform; it is a colorless liquid which possesses a density of 1.377 at -\- 15° C, and a boiling point of -f- 40° C. It is soluble in alcohol and ethyl ether. It is used in the form of a spray to produce local anesthesia, particularly in dental surgery. Eichardson introduced methylene chlorid as a general anesthetic in 1867. He reported that the vapor was pleasant to inhale and was not irritating; that the quantity of liquid required to produce anesthesia was 1 to 6 fluid drachms; that the required charge of air was 5 to 10 per cent; that the action was rapid, with short but rather acute spas- modic stage; and that insensibility was perfect. He found recovery to be rapid, and usually without bad symptoms; that vomiting occurred about once in six administrations; and that the animal temperature was reduced from 2° to 3° F. under deep anesthesia. To quote the con- clusions of Eichardson (Sci. Am. Suppl., No. 516, 8240) : "Pure meth- ene chlorid is one of the best anesthetics, but not free from danger. The deaths from it have been estimated at 1 in 7,000 administrations." Eegnault and Villejean (Compt. rend., 100, 1146) reported that methy- lene chlorid, like carbon tetrachlorid, but unlike chloroform and methyl chlorid, exerted a poisonous action when inhaled. See, however, Carbon Tetrachlorid. Methylene chlorid is said to be less toxic than chloroform (Francis and Fortescue-Brickdale's "The Chemical Basis of Pharmacol- ogy," 1908, 95). It cannot yet be regarded as a safe anesthetic. For cases of death from the inhalation of methylene dichlorid, see Brit. Med. J., Oct. 23, 1869; ibid.. May 7, 1870; ibid., April 29, 1871; ibid., Sept. 16, 1871; ibid., Aug. 31, 1872; ibid., Oct. 12, 1872; ibid., Oct. 19, 1873; Lancet, Dec, 1874; Brit. Med. J., July 24, 1875; Med. Times and Gaz., Sept. 22, 1877; iUd., June 23, 1877; and Brit. Med. 778 ANESTHESIA J ., March 2, 1878. While Morgan used this agent 1,800 times without a single accident (Brit. Med. J., Jan. 4, 1879), it will thus be seen that others have been less fortunate. Methylene Ether. — A mixture of equal parts of absolute ether and methylene bichlorid (Richardson, 1870). Eichardson (Sci. Am. Suppl., No. 516, 8240) described methylene ether as a colorless fluid, "more stable than the other anesthetic mixtures," the vapor of which was pleas- ant to inhale. He found that the quantity required for complete anes- thesia was 2 to 8 fluid drachms; that the action was steady and rapid, with a very slight spasmodic stage; and that recovery was quick, with few bad after-effects, and vomiting infrequent. To quote his conclu- sions : "An exceedingly good combination and deserving a further trial than it has received. Author administered it thirty times with most satisfactory results. One death occurred in the practice of Mr. Law- son Tait, from administration of a fluid supposed to be this mixture, but which contained choloroform in large proportion. In death of lower animals in this vapor, circulation survives respiration." On methylene ether, see also Richardson : Med. Times and Gaz., 1872, 2 ; and 1873, 1. For cases in which death occurred during its administration, see Phila. Med. Times, S, 718; Med. Times and Gaz., July 5, 1873; and Brit. Med. J., March 2, 1878, 290. Methylethyl. — A mixture of methyl and ethyl chlorids. See Meth- ethyl. Methylic-Ethylic Ether. — A mixture, proposed by Richardson in 1867, made by saturating ethyl ether with methyl ether gas. It was described by Richardson (Sci. Am. Suppl., No. 516, 8240) as a color- less fluid, very unstable and inflammable, possessing a density of 0.720. He reported that it was found to be extremely pleasant to inhale and that it showed all the effects of methyl ether, except that anesthesia was slower and more prolonged. "Would be among the most valuable of an- esthetics if it were more stable and practical in application." ITethyliuin Bichloratum Richardson. — See Methylene Ether. Methylium Oxyamidobenzoicum. — Para-Amido-m-oxybenzoic acid methyl ester, a local anesthetic. Methylpropylcarbinolurethane. — See Hedonal. Midy's Mixture. — This is described as a solution of 5/100 gram of subcutin, 1/10 gram of mercuric iodid, 1/10 gram of sodium iodid, 2/100 gram of sodium chlorid, and distilled water to make 1/100 c. c. Molecular Solution or Molecular Solution Mixture. — See "M. S." Monobromethane. — See Ethyl Bromid. Monochlorethane. — See Ethyl Chlorid. Monochloro-Ethylene Chlorid. — See Ethylene (Monochloro-) Chlorid. Morphin Hydrochlorid. — This compound has been employed as a local anesthetic with ether spray and for general anesthesia with chloro- A LIST OF ANESTHETICS 779 form vapor. Pitha stated (Wiener med. ]Yoch., 18G1, 25, 3(J) that, hav- ing unsuccessfully attempted for two hours to anesthetize a patient, first with a mixture of ether and chloroform, and then with chloroform alone, he finally inserted into the rectum a solution of the extract" of belladonna; the patient passed into a condition of anesthesia which per- sisted for twelve hours. In 1863 Nussbaum found that, by the hypo- dermatic injection of morphin at the commencement of inhalation, the anesthesia produced by chloroform could be prolonged for several hours. In this connection, see also Uterhart: Berl. Min. Woch., 1868, No. 32. Bernard ("Legons sur les Anaesthesiques," Paris, 1875) collected a large number of cases, illustrating the advantages connected with the combined administration of opiates and chloroform. As a result of his experiments in treating the same patients, sometimes with chloroform alone, and sometimes with chloroform and morphin, making an injec- tion about twenty minutes or half an hour before the operation, Kap- peler ("Ansesthetica," 209) concluded that the course of the resulting anesthesia did not materially vary under either set of conditions; he believed, however, that the character of the anesthesia was more tran- quil, and that the patient passed more rapidly, and with less excite- ment, into the stage of insensibility. See Scopolamin Hydrohromid and Pantopon. "M. S." (Molecular Solution) .—Weidig found that 119.5 gm. of "chemically pure" chloroform and 74 gm. of absolute ether, or, expressed in volume, 43.25 parts of chloroform and 56.75 parts of ether, mixed together, entered into '^chemical combination," representing a new an- esthetic. To quote Meyer (J. Am. Med. Assn., Peb. 29, 1903) : "It contains neither free ether nor free chloroform and has a boiling point of its own at + 125.6° P. ( + 52° C). We called this product molecu- lar solution (of chloroform and ether) or, abbreviated, 'M. S.' " In the first part of 1898 Meyer administered "M. S." for general anesthesia and found it to be an excellent narcotic. It was used by a num- ber of surgeons at the German Hospital in New York City in 1903. Por a discussion of the chemistry of "M. S.," see Anesthol (Meyer). Mylocal. — A solution containing cocain and antiseptics, for use as a dental local anesthetic. Nalicin. — A local anesthetic for dental purposes ; it consists of 1 gm. trinitrin and 1 gm. of cocain hydrochlorid in 100 gm. of a mixture of spiritus thymolic comp., alcohol, sodium chlorid, phenol, formaldehyd, and water. Narcoform. — Said to be a mixture of ethyl chlorid, 60 parts ; methyl chlorid, 35 parts; and ethyl bromid, 5 parts, which is the original soemnoform formula of Eolland (see Somnoform) but this cannot be definitely asserted. 780 ANESTHESIA Narcophin. — Narcophin, described as narcotin-morphin meconate, has been considered in tlie following contributions: Straub: Biochem. Z., Jfl, 419; Miinch. med. Woch., 1913, 1542. Schlimpert : Munch, med. Woch., 1912, 1544. Zehbe: 7&^c^., 1912, 1543. Hermann: Biochem. J., 39, 216, V. Issekutz : Pflugers Arch., lJf5, 415. Caesar: Biochem. Z., ^2, ISTo. 4. Zweifel: Monats. Geburtsh. u. Gyn'dk., 36; Erg'dnzungsh., 1912. von Stalewski: Therap. d. Gegenw., 1912. Narcosin. — A dental local anesthetic which contains extract of ham- amelis bark of high tannin content, "obtained by a peculiar process in an autoclave" (Eiedel's "Mentor," 1912, 186).. Flury {Z. angew. Chem., 26, 242) states that "Narkosin" is extract of hamaraelis containing narcotics. Narcotil (Narkotil) or Narcotile. — This inhalation anesthetic, also known as "Methylene Bichlorid," consisted of a mixture of methjd and ethyl chlorids. It was described as a colorless, very volatile and inflam- mable fluid, emitting a pleasant odor; and was said to be obtained by the action of hydrochloric acid upon a mixture of ethyl and methyl al- cohol. It was recommended by Eastham {Lancet, 1903, No. 4155, 1091) for general anesthesia, and was administered with the aid of Junker's inhaler, narcosis being effected within one minute. It was said that return to consciousness was not, as a rule, attended by headache, giddi- ness, or other unpleasant concomitants; but nevertheless the sale of the preparation was discontinued several years ago, as there were certain objections to its employment. According to Chem. Centr., 1903, 2, 307, "Narcotil" was a name used in England for "Methylene Chlorid" (q. v.). Narkose-Gemisch "Dr. Hirschlaff." — Each c. c. contains 0.05 gm. morphosan (morphin brommethylate) and 0.00015 gm. euscopol, dissolved in distilled water. It is offered to the trade in sterilized ampoules. Nealpon. — Flury (Z. angew. Chem., 26, 242) states that this prep- aration contains the alkaloids of opium. See Pantopon. Nerroeidin. — The same as Nervocidin (q. v.). Dumont ("Allge- meine u. lok. Anesthesie," 1903, 234) and others use this name instead of "Nervocidin," etymologically the correct term. Nervocidin. — The hydrochlorid of alkaloids contained in the Indian plant "Gasu-Basu" (Fharm. Ztg., ^7, 317). Nervocidin was isolated by Dalma, its anesthetic properties were discovered by a Hungarian dentist of Fiume, and it was studied by Fenyvessy in the Institute of Bokay, Budapest, pharmacologically. Nervocidin is described as a hy- groscopic, yellow amorphous powder, easily soluble in alcohol and ether. Applications of a 0.1 per cent solution are said to produce complete A LIST OF ANESTHETICS 781 anesthesia on mucous surfaces. It has been used in the eye in doses of 2 minims of a 0.3 per cent solution; stronger solutions are said to cause difficulties. For the cornea a 0.01 per cent solution is used. Xer- vocidin is used chiefly in dentistry to anesthetize painful pulpa, in the form of the hydrochlorid, which is very soluble in water. Hypodermic injections in animals produce paralysis of the motor centers and periph- eral nerves, ending in death. (See J. de V Anesthesie, 1902; Du- mont's "Allgemeine u. lok. Anaesthesie/' 1903, 231 and 235.) Neurocain. — Billets containing 1/12 grain (0.005 gm.) of cocain hydrochlorid for use as a local anesthetic in dental practice and in pressure anesthesia. ISTeurocain is said to be composed entirely of co- cain hydrochlorid, without excipient, and to have the advantage over cocain crystals that it dissolves "almost instantly" on contact with water ; the shape of neurocain is also said to render it peculiarly suitable for marginal and all other classes of cavities, but particularly for direct introduction into the pulp chamber. The billets are about 1/2 0th of an inch in thickness and i/gth of an inch long, and weigh 1/12 grain; they are formed from "absolutely pure" cocain hydrochlorid by special machinery. "No foreign matter of any nature is incorporated with the cocain, either to make the particles adhere or to regulate the weight." Nirvanin or Mrvanine. — This name was given by a German color works to a new product of theirs, the hydrochlorid of di-ethyl-glycocoll- meta-amido-ortho-oxy-benzoic-methyl-ester. NH.CO.CHjNCCaHfi), HO- COOCHs The preparation was stated to consist of colorless prisms, fusing at + 185° C. and freely soluble in water. The anesthetic properties of Orthoform {q. v.) suggested the desirability of transforming these sparingly soluble or sensibly acid bodies into freely soluble and non- irritant compounds which should be adapted for subcutaneous injection as well. Nirvanin was said to obviate these objections, and it was stated by Einhorn and Heinz {Miincli. vied. ^Voc^l., 1898, No. 49, 1553) that its principal utility consisted in its power of producing local anes- thesia for surgical operations by means of subcutaneous injections. It was said to share with Orthoform its enduring action, but to be less poisonous and at the same time to be antiseptic. Jouanin {Bull. gen. de Therap., June, 1898, 906; Eepert. de Pharm., 1899, 329) and Eeynier 782 ANESTHESIA (Rev. de Therap. Med.-chirurg., 1889, 505) studied the physiological action of nirvanin. The former regarded it as the least toxic of all bodies then employed for local anesthesia, since the lethal dose amounted to 0.7 gm. per kg. Eeynier confirmed the statements of Jouanin, but in- dicated, at the same time, that the anesthetizing power was visibly less than that of cocain. On the pharmacology of Nirvanin, see Didrichson: Wratscli^ 1900, No. 21. In surgical operations good results were wit- nessed by Boisseau (These de Bordeaux, 1899) and by Luxenburger (Miinch. med. Woch., 1899, Nos. 1, 2, and 38), the latter even going so far as to give nirvanin the preference over cocain and cocain mixtures in anesthesia by the infiltration and regionary methods. Holscher (Munch, med. Woch., 1899, No. 8, 247) and Schmidt (ibid., 1899, No. 38, 1255) employed nirvanin in regionary anesthesia and noted that its use gave rise to violent pains. Experiments on the use of nir- vanin in dental surgery were made by Dumont and Legrand: Rev. de Stomatol., March 20 and June, 1899; Stubenrauch: Miinch. med. Woch-, 1899, No. 38, 1255; Wittkowski: Odontol. Blatter, 1898, No. 15; Eoten- berger: Deut. zahndrztl. Woch., 1898, No. 38; Fricke, Schroder, and Carras: "Correspondenz f. Zahndrzte, 1899, No. 3, 264; Bounard: L'Odontologie, April 30, 1899, and others. The first three mentioned writers expressed a favorable opinion on the properties of nirvanin, whereas the last three joint authors condemned it, since its injection was found to invariably produce, in a more or less pronounced degree, pains in the puncture canals and their surroundings, and to give rise to edematic swellings liable to persist for days. In 1899 it was di- rected that regionary anesthesia according to Oberst be effected by means of a 2 per cent solution of nirvanin; that 0.1 to 0.5 per cent solutions be used in Schleich's method of infiltration; and that 2 to 5 per cent solutions be used in dental surgery. Marcus (Deut. zahndrztl. Woch., 1903, No. 39) published some observations respecting the use of nirvanin in dental surgery, as did Guadagnini (Bollett. delle scienze med., 1903, 77) ; these operators appeared to be favorably impressed with the anesthetic. Ouwarow (Wratsch, 1900, No. 23) found that nirvanin exercised an elective action upon the sympathetic nerve, since its use occasionally gave rise to irregular dilatation of the pupil, accelera- tion of the action of the heart, flow of tears, and ptyalism, Nirvanin is no longer on the market. Nitrogen. — While nitrogen cannot be regarded as an anesthetic, producing, as it does, simple, uncomplicated asphyxia, Sanderson, Mur- ray, and Turner (Brit. Med. J., June 13, 1868) experimented with the gas, finding that its primary effect was to accelerate the movements of respiration and circulation; respiration was then retarded and labored, while the pulse became slow and irregular. The pupils, which had been dilated, now became contracted. The countenance was pallid, and. A LIST OF ANESTHETICS 783 there was no appearance of cyanosis. Continued inhalation caused a renewed acceleration of the pulse, accompanied by retardation of respira- tion, and the production of a degree of insensibility sufficient for the painless extraction of a tooth. Nitrous Oxid.— See Chapter IV. Hunter (Eng. Pat. 7,343, 1885) proposed mixing nitrous oxid with vapor of alcoholic tinctures of hops, etc. Nopain. — This dental anesthetic is said to contain 1 part cocain hydrochlorid ; I/4 part phenol; 5 parts glycerin; 4 parts adrenalin solu- tion (1 : 1000) ; and 4 parts absolute alcohol. Nor-Cocain. — When nor-1-ecgonin has benzoyl and methyl groups in- troduced, as in ordinary cocain, nor-cocain, a powerful anesthetic, is pro- duced. This is, however, too toxic for practical purposes, owing, proba- bly, to the presence of the imid group (NH). Novadrin. — A solution containing novocain (0.015 gm.) and adre- nalin (0.00005 gm.), for subcutaneous injection. Novocain or Novocaine (Mon-hydrochlorid of para-amino-benzoyl- diethyl-amino-ethanol, NH2< ^ ^ OO.C2H4N(C2H5)2.HCl) . This compound produces a profound anesthetic action subcutaneously ; this passes ofE quite soon, leaving no symptoms of irritation. Le Brocq {Pharm. J., 82, 673) found that novocain is equal in anesthetic power to cocain, and that its toxicity and destructive action are much less. Experiments by Gros {Arch. exp. Path. Pharm., 67, 132), with the borate, bicarbonate, secondary phosphate, acetate, and chlorid of novo- cain, showed their narcotizing power to decrease in the order given. Novocain crystallizes from alcohol in colorless needles possessing a melting point of +156° C. It can be heated to +120° C. without decomposition. It dissolves in equal parts of cold water, and the solu- tion possesses a neutral reaction and may be boiled without decomposi- tion; it dissolves in cold alcohol in the proportion of 1:30. Caustic alka- lies and alkaline carbonates precipitate the free base from the aqueous solutions in the form of a colorless oil which soon solidifies to a crystal- line mass; on the other hand, sodium bicarbonate mixes with the water solution without producing a turbidity. Alkaloidal reagents, as potas- sium-mercuric iodid, picric acid, and iodo-potassium iodid solution, pro- duce precipitates even in very dilute water solutions of novocain. Phar- macological investigations show that novocain possesses the same action as cocain upon the peripheral sensory nerves, and that the 0.25 per cent solution suffices completely to anesthetize even the thick nerve trunks, as the sciatic nerve, in about ten minutes. It is said to produce no by-effect when applied locally, and that there are no symptoms of irri- 784 ANESTHESIA tation even when strong solutions are used. Experiments on animals showed, it is reported, that no^'ocain is about six times less toxic than cocain, far less toxic than any of the cocain substitutes, and the general effect on the system after its absorption is scarcely perceptible, neither the circulation nor the respiration being affected. Moreover, that the cardiac activity does not suffer, and that no mydriasis is produced. It has been shown that novocain not only does not reduce the action of suprarenalin, but increases it. The indications are the same as for cocain, and it is said to be useful in cases in which cocain is indi- cated. Dosage. — For infiltration anesthesia, solutions of 0.25 gm. (4 grains) novocain in 100 or 50 gm. (3.2 or 1.6 ounces) physiologic salt solution, with 5 or 10 drops of e|)inephrin solution (1:1000); for instillations and injections, solutions of 0.1 gm. (IV2 grains) novocain in 10 or 5 gm. (150 or 75 grains) salt solution, with or without 10 drops of epinephrin solution (1:1000). In ophthalmology, 1 to 5 to 10 per cent solution, in rhinolaryngology, 5 to 20 per cent solutions are recommended, with the addition of 6 to 8 drops of epinephrin solution (1:1000) to each 10 c. c. (160 minims). Internally, owing to its feeble toxicity, it may be given in doses up to 0.5 gm. (7^^ grains) to adults. The literature relating to novocain is quite extensive; a number of the references follow in chronological order: Braun, H. : Deut. med. Woch., 1905, No. 42. Biberfeld, Job. : Med. Klinih, 1905, No. 48. Heineke, H., and Lawen, A. : Deut. Z. f. Chir., SO, 180. Sachse, B. : Deut. zahndrztliche Woch., 1905, No. 45. Danielsen, Wilh. : Milnch. med. Woch., 1905, No. 46. Schmidt, Erhardt: Muncli. med. Woch., 1905, No. 46. Duhot : Ann. de la polidin. centrale de Bruxelles, 1905, No. 12. Krecke : Milnch. med. Wocli., 1906, No. 6, 287. Liebl, Fritz: Munch, med. Woch., 1906, No. 5. Cisler, Josef: Casopis Lel-.aruv Geshych (Prag), 1906, No. 5. Klein: Les Nouveaux Remedes, 1906, No. 3. Sonnenburg, Ed. : Von Leuthold-Gedenlcschrift, 1906, 2. Best, F. : Med. Woch., 1906, No. 10. Lucke, Eobert: Monats. f. Harnkranhh. und Sex. Tlygiene, 1906, 3. Mayer, Theodor. Dermatologische Z., 1906, 13, No. 3. Hermes, 0. : Med. Klinih, 1906, No. 13. Ciezynski, A. : Deut. Monats. f. Zahnheilk., Apr., 1906. Opitz: Milnch. med. Woch., 1906, No. 20. Willke, 0. : Medico, 1906, No. 19. Euler : Dmt. zahndrzil. Woch., 1906, No. 20. Gebb, H. : Archiv filr Augenheilk., May, 1905, 55, Nos. 1 and 2. Lazarus, Paul: Z. f. physikal. und didtet. Therap., 1906, 10, No. 2. A LIST OF ANESTHETICS 785 Freemann: Dermatol. Zentralb., 190G, No. 8. Brunner: Munch, med. Woch., 1900, No. 23. Pinet and Jeay: L'Odontologie, May 30, 1900, No. 10. Fischer, Guido : Deut. Monats. f. ZahnheiUc, June, 190G. Graeser, Carl: Jahresher., 1905 and 1906, d. Deut. Kranken. Nea- pel, 42. Haug: "Therap. von Ohralfektionen," Archiv f. Olirenlieilk., 190G, 69. Misch, Julius: Oesterreichisch-Ungarische Yierteljahres. f. Zahn- heilk., July, 1906, No. 3. Freund, Eich. : Deut. med. Woch., 1906, No. 28 ; and Milnch. med. Woch., 1906, No. 30. Stieda, A. : Munch, med. Woch., 1906, No. 30, 1490. Katz, Leo : Deut. med. Woch., 1906, No. 36. Hoppe: Die drztliche Praais, 1906, No. 16. Lindenstein: Deut. med. Woch., 1906, No. 45. Blondel, Paul: Eev. de Therap. Med.-chir., 1906, Dec. 23. Hamecher, Hans: Odontol. Blatter, 11, Nos. 7-8. Hoffmann, C. : Miinch. med. Woch., 1906, No. 52. Eemien, Carl: Allgem. med. C entral-Z eitung , 1906, No. 8. Eegnier : Bull, de VAcad. de Med., 1907, 484. Nast-Kolb: Miinch. med. Woch., 1908, No. 13. Struthers: Ednh. Med. J., Feb., 1908. Bier, August: Archiv f. hlin. Chir., 86, No. 4; Surg. Gynec. and Obstet., Nov., 1908. Cramer: Dissert., Freiburg, 1908. Stoekel, W. : Central, f. Gynak., 1909, No. 1. Albright, J. D. : "Albright's Office Pract.," July, 1909. Hahn: Deut. zahndrztl. Woch., 1909, No. 5. Nystrom: Zentralb. f. Chir., 1909, No. 5. Blum : Z. f. Urologie, 1909, No. 2. Bolze: Zahntechn. Rundschau, 1909, No. 9. Erhart : Zahntech. Rundschau, 1909, No. 1. Prinz : Zahndrztl. Rundschau, 1909, Nos. 4-10 ; and Deut. zahndrztl. Zeit., 1909, No. 10. Sieber: Miinch. med. Woch., 1909, No. 10. Bier : Berl. klin. Woch., 1909, No. 11. Le Brocq: Brit. Med. J., 1909, No. 2517, 783. Petrow: Zentralbl. f. Chir., 1909, No. 14. Baarnhielm: Allmdnna Svenska Ldkartidningen, 1909, No. 11. V. Lichtenberg: Deut. med. Woch., 1909, No. 16. Busse: Therap. der Gegenwart, 1909, No. 5. Spisharny: Russkiy Wratsch, 1909, No. 9. Braun: Deut. med. Woch., 1909, No. 16. 786 ANESTHESIA Euprecht: Monats. f. OhrenlieilJc. unci Laryngo-Bliinol., 1909, Nos. 3 and 4. Braun: Beitr. z. hlin. Chir., 1909, 62, No. 3. Diiwawis: Prakt. Wratscli, 1909, No. 11. Scheff: Osterr.-ungar. Vierieljahressch. f. Zalinlieilh.j, 1909, No. 1. Fischer : Deut. zahndrztliche Woch., 1909, No. 23. Lemire and Ducrotoy: "Eecueil de memoires et observations sur I'hygiene et la medecine veterinaires inilitaires," 1908, 10. Canny Eyall: The Clin. J., 1909, No. 871. Hammer: Deut. militdrdztliche Z., 1909, No. 11. Gros: Munch, med. Woch., 1910, No. 39. Lawen : Ihid. Krecke: Milnch. med. Woch., 1910, No. 26, 2447. Gross: Gyndkol. Rundschau, 1910, No. 17. Kraatz: ZentralU. f. Gyndkol, 1910, No. 22. Kutscher: Deut. m,ed. Woch., 1910, No. 24, 1129. Biinte-Moral : Deut. Monats. f. Zahnheilk., 1910, No. 2. Senator: Munch, med. Woch., 1910, No. 10, 524. Schliiter: Klin. Monatshl. Augenheilk., Ji-B; Biochem. Centr., 8, 900. Moller : Deut. zahndrztl. Woch., 1910, No. 35 ; 1911, No. 16. Gros: Arch. exp. Path. Pharm., 1912, 67, 132-6. Prinz: Dental Summary, Feb., 1912; Pharm. J., 88, 779. Novocain, Adrenalin, and Sodium Bicarbonate. — Novocain, adren- alin, and sodium bicarbonate solutions have been proposed for renal operations. See Milnch. med. Woch., 1911, No. 26; Therap. Gaz., Aug. 1.5, 1911. Novocain Bicarbonate Solutions. — Gros (Milnch. med. Woch., 1910, No. 39) demonstrated that, in animals, solutions of salts of cocain, novocain, alypin and eucain, to which an alkali had been added, showed a considerable increase in their anesthetic properties. In practice, sodium, bicarbonate was recommended for this purpose. For local anesthesia Lawen (ibid.) tested this method especially with novocain. He found on using a solution of novocain, sodium chlorid, and sodium bicarbonate that the resulting anesthesia occurred earlier than was the case when novocain solution was employed, while it continued for a far longer time. He gave formulas for preparing three different strengths of solu- tions to be used for sacral, regional, and dental anesthesias. It is said that for pure infiltration anesthesia no special advantages are to be obtained from solutions of novocain bicarbonate. Novocain Nitrate (Novocainse Nitras). — Novocain nitrate is 1-para- aminobenzoyl-2-diethylamino-ethane nitrate [C6H4NH2C.00;G2H4.N (C2H5)2.HN03^ CigHjiOsNg], the nitrate of p-aminobfinzoyl(iiethyl- aminoethanol, the base contained in novocain. Novocain nitrate is bb- tained in small colorless and odorless crystals, soluble in water arid al- A LIST OF ANESTHETICS 787 cohol. The aqueous solution is neutral in reaction. Melting point, + 100°-102'' C. (212-215° F.)- If 0.1 gni. novocain nitrate is dissolved in 1 c. c. concentrated sulphuric acid and a solution of ferrous sulphate is carefully floated above it, a brown zone is formed at the surface of contact of the two solutions. One part of novocain nitrate dissolved in 10 parts water and acidified with nitric acid should yield no precipitate upon the addition of silver nitrate solution. Actions and Uses. — As for novocain, it may be prescribed in com- bination with silver salts, with which it forms no precipitate. Dosage. — Used in 3 per cent solutions. Novocain-Suprarenin Solutions. . 5 per cent solution = Tablet A in 2.5 c. c. water. 2.0 " " " = " B " 5 " " K rj a it it _ II /~i u 1 (I a 10.0 " " " = " D " 2 " " 2.0 " " " = " E " 1 " " Novocain-Suprarenin Tablets. — A. — 0.125 gm. novocain -j- 0.00016 gm. suprarenin borate, for infiltration anesthesia; B. — 0.1 gm. novocain -\- 0.00045 gm. suprarenin borate; C. — 0.05 gm. novocain -\- 0.000108 gm. suprarenin borate, for medullary anesthesia; D. — 0.2 gm. novocain -\- 0.00015 gm. suprarenin borate -|- 0.09 gm. sodium chlorid, for dental operations; E. — 0.02 gm. novocain + 0.000015 gm. suprarenin borate -(- 0.009 gm. sodium chlorid, for dental operations. Novoconephriii. — jSTovocain, 0.018 gm.; paranephrin, 0.00007 gm. ; with a trace of thymol, in physiological salt solution, 1.25 gm. An in- jection-anesthetic in dentistry. Novo-Dentaesthin. — This dental local anesthetic contains in 1 c. c. of a physiological salt solution 0.01 gm. beta-eucain lactate, 0.015 gm. novo- cain, and 0.05 gm. of synthetic suprarenin. Novorenal. — The 0.25 per cent solution contains 0.0125 gm. of novo- cain, 5 gm. of physiological salt solution (NaCl), and 0.00001625 gm. suprarenin hydrochlorid ; the 0.5 per cent solution contains double the above quantities of novocain and suprarenin; the 1 per cent solution contains 0.01 gm. novocain, 1 gm. of physiological salt solution, and 0.00009 gm. of adrenalin hydrochlorid ; the 2 per cent solution contains 0.02 gm. of novocain, 1 gm. of physiological salt solution, and 0.00009 gm. of suprarenin hydrochlorid. These solutions are employed as local anesthetics; novorenal 2 per cent is most used by dentists, and the ex- periences are reported to be very good. Novorobiol. — See Rohiol. Nussbaum's Mixture. — Alcohol, 1 part; chloroform, 1 part; and ether, 3 parts. Mixed. See Potter: "Mat. Med. Pharm. Therap.," 10th ed., 88. 788 ANESTHESIA Obalgo. — A dental local anesthetic of unknown origin. Obtundo. — A dental local anesthetic consisting of chloretone, cocain, nitroglycerin, thymol, menthol, and oils of wintergreen, eucalyptus, and cloves. Octane. — This hydrocarbon, which is contained in commercial ligroine in crude petroleum, produces an anesthesia similar to that caused by Hexane (q. v.) ; in addition, according to Versmann, there is a tend- ency to vomiting. The unsaturated hydrocarbons ethylene, propylene, and butylene are said to have a very similar action. Odiot. — Tincture of benzoin, with balsam of Peru and oil of cloves. Used in odontalgia. Oil Absinthium, or Oil Wormwood. — This oil possesses anesthetic properties. Omnopon. — See Pantopon. O-phthaloyl-bis-methylecgonin. — Einhorn and Klein (Ber., 1888, 21, 3335) have shown that this compound possesses a physiological action similar to that of cocain. Opiopon. — According to Flury {Z. angew. Chem., 26, 242), this preparation contains the alkaloids of opium. See Pantopon. Opon. — According to Flury {Z. angew. Chem., 26, 242), Opon is a morphin-free Pantopon (q. v.). Orthoform (Orthoform-Proper; Para-amido-meta-oxybenzoic acid methyl ester, HjN<(^ ^COOCH,). See Ortho form-New, which is a finer, whiter, more homogeneous powder and is less expensive than orthoform-proper. Like orthoform-new, orthoform-proper exercises its full local anesthetic action even in a 10 to 20 per cent mixture with amylum or talcum. It is very slightly soluble and is also but feebly toxic. It is said, however, that it is only active when directly applied to the nerve endings, and that it is useless when applied to the unbroken skin or mucous membranes. The soluble hydrochlorid of orthoform-proper is not used in practice, owing to the fact that its injection produces pain. According to Francis and Fortescue-Brick- dale ("The Chemical Basis of Pharmacology," 1908, 310), orthoform has also been observed to produce severe dermatitis of an erythematous, pustular, or even gangrenous type. Orthoform-New ( Meta-amido-para-oxybenzoate of methyl). — Ortho- form-New is methyl meta-amino-para-oxybenzoate, C«H3.NH,.0H.C00(CH3), 3 : 4 : 1 = CgHAN, the meta-amino-para-oxybenzoic acid ester of methyl alcohol. It is pre- pared by the nitration of para-oxybenzoate of methyl and reduction of the nitro product obtained. A large number of bodies have been pre- A LIST OF ANESTHETICS 789 pared which resemble orthoform, but only a few are of any practical use. It is obtained in a fine, white, crystalline powder, neutral in reac- tion, and melting at + 141° to 143° C. (285.8° to 289.4° F.), odor- less and tasteless. It is scarcely soluble in water, but is soluble in 5 or (5 parts of alcohol and 50 parts of ether. It is decomposed by boiling with water, or by warming with alkalies or their carbonates, into methyl alcohol and paroxybenzoic acid. When crystallized from chloroform it sometimes assumes the form of white crystals melting at -|- 110° to 111° C. (330° to 231.8° F.), returning, on melting, to the ordinary form. The filtrate obtained after shaking a small portion with water produces a fugitive color with ferric chlorid, and should not give a reaction with silver nitrate. A solution of 0.1 gm. in 2 c. c. of water by the aid of hydrochloric acid is colored yellowish red on addition of sodium nitrate, and then deposits a yellow precipitate, deepening to red on exposure to the air. It is decomposed by heating with water; it is incompatible with al- kalies and their carbonates. Orthoform is also incompatible with silver nitrate (see Bock: Therap. Monatsh., 1898, 413), the organic silver albuminoid preparations, formaldehyd, potassium permanganate, ferric chlorid, antipyrin, and bismuth subnitrate. It may, however, be com- bined with solutions of mercuric chlorid, tincture of iodin, turpentine, solutions of copper sulphate, iodoform, dermatol, zinc oxid, europhen, aristol, calomel, and salicylic acid. It is also applicable in 3 to 5 per cent solutions of phenol, and with lysol and cresol solutions. Its hydro- chlorid is soluble, but irritant. Actions and Uses. — Orthoform-New is a local anesthetic, resembling cocain in its local action, but not penetrating the tissues on account of its insolubility. It has practically no action on the unbroken skin, except for a slight irritation which it produces about the place of appli- cation. It is somewhat antiseptic and practically non-toxic in the usual doses. It is used internally to relieve the pain of gastric ulcer. Since it acts only on ulcerated surfaces, the relief of pain has been assumed to be evidence of the existence of an open ulcer. It has been applied lo- cally as an analgesic to wounds of every description. It has been used in dentistry, in nasal catarrh, hay fever, etc. Orthoform paralyzes, just as cocain, all the peripheral sensory nerve endings and nerve trunks with which it is brought into direct contact. Therefore, because of its insolubility, it can only exercise its properties when applied to wound surfaces where the nerve endings are exposed, and does not penetrate the tissues. Its antiseptic action is weak. Heinz determined experimentally, and this point has been confirmed by clini- cal work, that the drug exerted practically no toxic action on the econ- omy at large when administered in the doses recommended. Cf. Soulier and Guinard : Repert. de Fharm., 1898, 420. Owing to the slow solu- 790 ANESTHESIA bility of orthoform, only small quantities are absorbed at a time, thus prolonging anesthesia for hours or days. It is said to be applicable whenever pain is in evidence, and to be of value as a sprinkling powder, pure or mixed with some bland powder, in solution in alcohol, ethyl ether, or collodion, and in an ointment. Dosage. — Internally, 0.5 to 1 gm. (8 to 15 grains) in emulsion; lo- cally, in substance as a dusting powder or mixed with milk sugar for insufflation, dissolved in ether and mixed with oil for penciliugs, or as a salve with wool fat, etc. The following are some of the references to the literature of ortho- form. Einhorn and Heinz : "Orthoform ; ein Lokalanasthetikum f iir Wundschmerz, Brandwunden, Geschwiire usw.," Milnch. med. ^Vocli., 1897, No. 34; No. 37, 555. ■ Neumayer: tJber Orthoform," Miincli. med. Woch., 1897, No. 44, 1230. Klaussner: "tJber Orthoform," Miinch. med. Woch., 1897, No. 46, 1289. Boisseau: "De I'orthof orme ; son emploi en oculistique," Gaz. liehd. d. Sciences med. d. Bordeaux, 1897, G03-607. Kallenberger : "tJber Orthoform," Inaug. -Dissert. Miinchen, 1897. Lichwitz and Sabrazes: "L'Orthoforme comme anesthesique et comme antiseptique," Bull, med., Nov., 1897, No. 94. Tschernogoubov : "Orthoforme pour injections souscutanees," Sem. med., 1897, No. 16. Hirschbruch: "Orthoform," Berl. Uin. \Yocli., 1897, No. 51. Boisseu: "L'Orthoforme en laryngologie et en stomatologic," Gaz. Jiebd. d. Sciences med. d. Bordeaux, Jan., 1898, 39-41; also, Presse med., 1898, 89. Yonge: "Treatment of Painful Ulcerations," Brit. Med. J., Feb., 1898; see, also, Canadian J. Med., 1898, No. 3. Cumston: Boston Med. and Surg. J., Mar. 24, 1898. Kindler: "Orthoform," Fortsch. d. Med., Apr., 1898, No. 7. Bernould and Garrel: "L'Orthoforme en laryngologie," Lyon med., 1898, No. 13. Kallenberger: "tJber Orthoform," Berl. Min. Woch., 1898, No. 12; I naug. -Dissert., Miinchen, 1898. Dreyfuss: "Kombination von Infiltrationsanasthesie nnd Ortho- form," Munch, med. Woch., 1898, No. 17. Nogoues: "L'Orthoforme dans les affections douloureuses de la vessie," Annales des maladies des organes genito-urinaires, Paris, 1898, 547. A LIST OF ANESTHETICS 791 Fromaget: "Orthoform bei Augenaffektionen," Berl. Iclin. Woch., 1898, No. 9. Ginestoux: "Acide arsenieux et orthoforme dans le traitement du cancer epithelial," Sem. med., Apr., 1898, No. 20. Cerry and Tourecek: "Emploi de I'orthoforme," Sem. med., Apr. 13, 1898. Bonnard: "L'Orthoforme et le chlorhydrate d'Orthoforme en art dentaire," L'Odontologie, May 30 and June 15, 1898. Brocq: "Accidents produits par I'orthoforme,' Sem. med., 1898, No. 17. Bornstein: "Orthoform," Zahndrzt. Bunds., May 15, 1898, No. 306. Lichtwitz: "Traitement de la rhinite vaso-motrice (hydrorrhee nasale, fievre des foins) par I'orthoforme," Le Bull, med., 1898, No. 7; Arch, interuat. Laryngol., 1898, No. 1. Loeb: "Orthoform als Anasthetiknm bei intramuskularen Injek- tionen," Monats. f. praJct. Dermatol., Jan. 27, 1898. . Jessen : "Orthoform," Deut. zahndrzt. Woch., 1898, No. 10. Blondel: "L'Orthoforme en gynecologic," Rev. d. Therap., May, 1898, No. 10. Manquat: "Deux nouveaux anesthesiques locaux, I'orthoforme et la nirvanine," Bull, med., 1898, 984. Pozzi: "L'Orthoforme en gynecologic," Le Scalpel, May, 1898, No. 46. Mosse: "Verhalten des Orthoforms im Organismus," Deut. med. Woch., 1898, No. 26; see, also, Klin.-Therap. Woch., 1898, No. 25. Mosse, Herzfeld, Jastrowitz, v. Leyden, Goldscheider, Frankel, Ehrlich : Discussion : "Verhalten des Orthoforms in Organismus," Allge. med. Central-Zeit., June, 1898, No. 47; Deut. med. Woch., 1898, No. 17. Bezold: "Orthoform," Miinch. med. Woch., 1898, No. 26. Gianelli : "L'Orthoformio in ginecologia," Archiv. Ital. di Ginecol., 1898, 508-511. Schech: "Orthoform," Miinch. med. Woch., 1898, No. 26. Fink: "Orthoform in der Ehino-Laryngologie," Arztl. Praxis, 1898, No. 20. Jessen: "Orthoform," Jahresbericht der Poliklinik fiir Zahnkrank- heiten, Strassburg, 1898-1899 ; Deut. zahndrztl. Woch., 1898, No. 10. Ivorn: "Orthoform bei Prurigo und bei Herpes Zoster," Die drztl. Praxis, July, 1898, No. 13. Hecker: "tJber Orthoform," Inaug. -Dissert., Berlin, July, 1898. Bock: "Beitrage zur Kenntnis des Orthoforms," Therap. Monatsh., 1898, 413. 792 ANESTHESIA Eotenberger: "Orthoform und 'Orthoform neu' und Nirvain/' Deut. zahndrz. Woch., 1898, No. 38. Klaussner : "Uber Orthoform und 'Orthoform neu,' " Munch, nied. Woch., 1898, Xo. 42, 1338. Kassel: Uber Orthoformemulsion," Therap. Monatsh., Oct., 1898, 556. Heinzel : "Uber Orthoform," Wiener Min. Woch., 1898, No. 48. Wohlgemuth: "Uber Orthoform," Deut. med. Woch., 1898, No. 44. Hanszel: "Orthoform," Wiener Min. Woch., 1898, No. 49. North : "Orthoform as a Local Anesthetic, Analgesic, and Antisep- tic," Am. Med. Compend., Nov., 1898, Maygrier and Blondel: "Zur Behandlung der Ehagaden der Brust- warze bei stillenden Frauen," Revue de Therap., 1898, 797. Apfelstadt : "Orthoform," Deut. zahndrzt. Woch., 1898, No. 40. Hildebrandt: "Beitrag zur Orthoformanasthesie," Deut. med. Woch., 1898, No. 48; Therap. Beil., No. 12, 95. Lobisch : "Orthoform," Enzyhlopddische Jahrh., 1898, viii. Lipowski: "Larynxerkrankungen," Therap. Monats., 18, No. 12. Deniges : "Sur les orthoformes, caracteres et differences," Bull. d. la Soc. d. Pharmacol, d. Bordeaux, Dec, 1898. Ducray: "L'Orthoforme et ses indications en laryngologie," Inaug.- Dissert., Lyon, 1898. Herzfeld : "Verhalten des Orthoforms im Organismus," Allge. med. Centr.-Ztg., June, 1898, No. 47. Teisseire : "Traitement des gergures et crevasses du sein par d'ortho- forme," Inaugural-Dissertation, Paris, 1898; also, Sem,. med., 1898, No. 57, 226. Kionka : "Uber neuere Arzneimitte," Therap. der Gegenwart, 1899, No. 1. Holmes: "The Use of Orthoform in Surgery," Woman's Med. J., Jan., 1899, No. 1. Johnson : "Orthoform," Woman's Med. J., 1899, No. 1. Maygrier: "Treatment of Fissures of the Nipples," Med. Press, Jan. 25, 1899. Danlos: "Orthoform," La Presse med., Jan. 14, 1899; "Injections de calomel additionees d'orthoforme a titre d'analgesique," J. d. Malad. Cutan. et Syphilit., 1899, 00. Epstein : "Uber Orthoform, bezw. 'Orthoform neu' als Zusatz zu Quecksilberparaffin-Emulsionen," Dermat. Centralhlatt, February, 1899, No. 5. Goppert : "Orthoform," Fortsch. der. Med., 1899, No. 35 ; "Ortho- form," Jahrhuch f. Kinderheilk., N. F., Feb., 1899, No. 49. Asam: "Erfahrungen mit Orthoform," Miinch. med. Woch., 1899, No. 8, 252. A LIST OF ANESTHETICS 793 Cheatham: "A Note on Orthoform," Amer. Therap., Feb., 1899, No. 8. Mailland: ''Accidents provoques par I'orthoforme employe comme topique des plaies," Province med., 1899, 135. Meyer: Laryngologist, March, 1899. Sims: "Experience with Orthoform," Therap. Prog., 1899, No. 3. Dickenson: "Orthoform in Rectal Affections," Therap. Prog., 1899, No. 3. Crisand: "Clinical Note on Orthoform," Therap. Progress, 1899, No. 3. V. Zander: "Das Orthoform in der Laryngologie," Gharite-Ann., March, 1899, 23. Freudenthal: "Behandlung des Hustens und der Tuberkulose," Monat. f. Ohren-, Kehllcopf-, Nasen- und Rachenlcrankheiten, 1899, No. 3. Schroppe: "Orthoform-Exanthem," Petersburger med. Woch., Mar., 1899, No. 12; No. 13, 100. Kindler: "Weitere Mitteilungen iiber den Gebrauch von Ortho- form," Fortsch. der Med., 1899, No. 7. Miodowski: "Orthoform," Milnch. med. Woch., 1899, No. 12, 382. Boisseau: "Contribution a I'etude de I'orthoforme," Inaug. -Dissert., Bordeaux, Mar. 24, 1899. Albertin: "Intoxication par I'orthoforme employe comme topique dans le pansement des plaies," Lyon med.. May, 1899. Darier: "De Taction analgesiante de I'orthoforme dans certaines affections oculaires," La Cliniq. Ophthal., Apr., 1899, No. 8. Brocq: "De I'orthoforme en dermatologie," J. d. Pratic, 1899; Presse med., 1899, No. 30 ; "Intolerance par I'orthoforme," Soc. frang. d. Dermatol., Paris, Apr., 1899. Dauchez : "Progres. med.. May 20, 1899. Brocq and Besnier : "firuptions orthoformiques," Soc. frang d. Dermatol., Paris, April, 1899. Brocq and Thibierge: Gaz. hebd. de Med. et de Ghir., 1899, No. 32. Deniges : "Priifung des Orthoforms," Les Nouveaux Eemedes, 1899, 400. Wunderlich: "Zur Anwendung von Orthoform," Milnch. med. Woch., 1899, No. 40, 1296. Gomberz: "tJber Versuche mit einigen neuren Mitteln," Monat. f. Ohrenheil, 1899, No. 6, 256. Kassel: 'Orthoform-Neu," Monat. f. Ohrenheil., 1899, No. 6. Dunogier: "L'Orthoforme," J. de Med., June, 1899. Soulier and Guinard : "Contribution a I'etude pharmacodynamique de I'orthoforme," Archiv. Jnternat. d. Pharmaco. et d. Therap., 1899, 6. Bleuler: "Orthoform," Neurolog. Gentral, 1899, No. 14. 794 ANESTHESIA Wright: "The Prevention of Hayfever/' N. Y. Med. J., May 6, 1899. Ott: "Orthoform," Med. Arena, Sept., 1899. Madden: "Observation on Uterus Cancer Treatment," Dublin J. Med. 8ci., 1899, 409. Maire: "Behandlung der Papilla fissurata," Zentralh. f. Gynakol., Aug., 1899, No. 32. Salzer: "Orthoform bei Augenaffektionen," Die ophthal. Klinih, Sept., 1899, 257. Stubenrauch, Klaussner, Gossmann, Krecke, Moritz: "Diskussion iiber Orthoform"; Auszug: Miinch. med. Woch., 1899, Nos. 38, 39, Seite 1254. Whien : "Des eruptions dues a I'orthoforme," Bull. d. VHopital frang. d. Tunis, 1899, 243. Mirabeau: "Orthoform," Zentralbl. f. Gynakol, 1899, No. 11; Monat. f. Gehurts., 1899, 9. Decker : "Dermatitis Following the Use of Orthoform," N. J. Med. J., 1899, 780. Sauer : "Orthoform-Idiosynkrasie ?" N. Y. Med. Monat., 1899, No. 12. Bardet: "Note sur les modes d'administration de I'orthoforme et sur quelques applications," Bull. gen. d. Therap., Feb., 1900, 262. Blondel : "Traitement des crevasses du mamelon par I'orthoforme,'^ Soc. d. Therap., Feb., 1900. Dejace: "Orthoforme," Le Scalpel, July, 1900, No. 5. Luxenburger: "Experimentelles und Klinisches iiber Orthoform," Miinch. med. Woch., 1900, Nos. 2, 3, 48, and 82. Sprague : "Orthoform Facts," Am. Therap., Sept., 1900, No. 3. Thelberg : "Treatment of Anal Chancroids," N. Y. Med. J., May 26, 1900. Norbury : "Orthoform in the Treatment of Epithelioma," Med. Fort- nightly, March 26, 1900. Helouin: "L' Orthoforme," Bull, des Sci. pharmacol., Nov., 1900, No. 11. Gleason: Internat. Med. Mag., Oct., 1900. Friedlander: "Orthoformvergiftung," Therap. Monat., Dec, 1900, No. 12, 676. Euhemann: "Ein Fall von Orthoformvergiftung," Therap. Monat., Dec, 1900-1901, No. 12. Lang: "Erfahrungen mit Orthoform und Nirvanin," Zahndrzt. Rundschau, 1900, 6359-6360. Plique : "L' Orthoforme," La Presse med., 1900, 204-205. Vacek: "Sur I'orthoforme," Casopis Laharuv. CesJcych, Prag, 1900, 154. A LIST OF ANESTHETICS 795 Villa: "Contribution a I'etude experimentale et dinique de I'ortho- forme,"' Inaugural-Dissertation, Lyon, 1900. Villa: "A propos des accddents produits par Forthoforme," Echo med. de Lyon, 1900, 161-171. Vogt: "Traitement de la periode eruptive du zona par les applica- tions d'orthoformc," Bull. gen. d. therap., 1900, 576. Garnault: "Traitement de la tuberculose par la viande crue et par les injections intratracheales d'orthoforme," Bull. d. la Soc. d. Therap., Jan., 1901. Heineck: "Newer Local Anesthetics. Holocain, JSTirvanin, Ortho- form," The Bacillus, Jan., 1901. Brewster: "A Eeview of Some of the Modern Medicinal Prepara- tions Used in Dentistry," Items of Interest, Jan., 1901, No. 1. Spiess : "Ein neuer Gesichtspunkt in der Behandlung des Keuch- hustens," Miinch. med. Woch., Apr., 1901, No. 15, 596. Spiess: "Ein neuer Gesichtspunkt in der Behandlung des frischen SchnupfenSj" Archiv f. Laryngol., 1901, 12, No. 1. Colleville : "Sur un cas de nevralgie sacro-lombaire traite par des injections epidurales de guaiacol orthoforme," Union med. du Nord-est, May 30, 1901. Graul: "tjber Nebenwirkungen des Orthoforms," Deut. med. Woch., 1901, No. 24, 390. Friedrich: "Sammelreferat iiber neuere Arbeiten aus dem Gebiete der Nasen und Kehlkopfkrankheiten," Fortsch. der Med., Sept., 1901, No. 25. Siebourg: "Beitrag zur Behandlung des Pruritus vulvae," Zentralhl. f. GyndJcol, 1901, No. 26. Hornberger: "tJber Orthoform," Therap. Monats., October, 1901, 519. Boennecken: Prager med. Woch., 1901, No. 37. Memmi: "L'Orthoformio per la diagnosi dell'ulcera gastrica," Riforma med., 17, Nos. 112-116. Dubreuilh : "Des Eruptions orthoformiques," La Presse med.. May 18, 1901, No. 40. Holger-Mygind : "Lehrbuch der Krankheiten der oberen Luf twege," 1901. Bouveyron-Siraud : "Orthoform innerlich." Sem. med., 1901, No. 50, 400. Horn: "Ein Fall von mit Menthol-Orthoform-Emulsion behandel- tem Pharynx," N. Y. Med. Monat., 1901, 134. Solis-Cohen: "Orthoform Lozenges to Mitigate Odynophagia," Am. Med., Nov. 9, 1901. Odenthal: "Schadliehe Wirkung des Orthoforms," Deut. zahndrzt. Woch., 1901, 1623. 79a ANESTHESIA Heryng: "Zur Anwedung des Orthoforms,'^ Gazeta Lekarska, 1901, ^0. 39. V. Tovolgyi : "Uber di Behandluiig der Kehlkopftuberkulose, mit Eiicksicht auf die neuren Heilmittel/' Tlierap. der Gegenwart, Mar., 1902. Melenowski : "Ein Fall von Orthoformvergiftung," Gazeta LeTcarsJca, 1901, No. 48. Eriedliiuder: "Eiitgegnuiig auf den Artikel von Homberger," TTierap. Monat., Nov., 1901. Haug: "Orthoform gegen die Schmerzen bei Furunkeln des Meatus auditorius," Monats. f. Ohrenheillc, 1901, No. 12. Homberger: 'SSchlussbemerkung liber Orthoform," Tlierap. Monats., Feb., 1902. Wright: Med. Neivs, Jan. 19, 1902. Bowen: "Orthoform Eruptions," Boston Med. and Surg. J., Mar. 20, 1902. Spiess; "Die Heilwirkung der Anasthetika,'' Zentralhl. f. innere Med., Mar., 1902, No. 9. Veis: "Ein Beitrag zum Verlaufe von Larynxtuberkulose in der Graviditat," Monat. f. Ohrenheillc., 1902, No. 4. Freytag: "tJber Kehlkopftuberkulose," Munch, med. Wocli., 1902, No. 19. Wassermann : "tJber Nebenwirkungen des Orthoforms und ihre bisher ungelkliirte Atiologie," Von Leyden-Festschrift, 1902, 2, 317. Dalche : "Les leucorrhees virginales et leur traitement," Gaz. med. Beige, 1902, No. 41. Czaplicki : "Orthoform," Przeglad Lelcarshl, Ivraku, 1902, 305-30G. Gardner and Wilson: "Clinical Eeport of Some Genito-Urinary Cases," Buffalo Med. J., July, 1902. Schalenkamp: "Zur Frage der schadliclien Nebenwirkungen des Orthoforms," Beichs-Med.-Anzeiger, 1902, No. 16. Murdoch : "Orthoform in the Diagnosis of Gastric Ulcer," iV. Y. Med. J., Nov. 29, 1902, No. 22. Plesch: "A Tiidovesz es Tlineti Kezelese," Budapest, 1902, 41. Aveline : "Contribution a I'etude de I'orthoforme," Monograph, Paris, 1902 ; also, Gaz. des Hop., 1903, 20. Iiobertson: /. Am. Med. Assn., Jan. 17, 1903. Luntz : "Zur Bchandlung der Fissuren des Anus," St. Petershurger med. Gesells. (Arztl. Bunds., 1903, No. 25). Dumont: "Handbuch der allgemeinen und lokalen Anasthesie," Berlin and Wien, 1903, 230. Dickinson: Detroit Med. J., Aug., 1903. Cohn: "Tuberculosis of the Larynx/' Occidental Med. Times, Sept., 1903. A LIST OF ANESTHETICS 797 Mayer und Thiesen: "Discussion of a paper, "The Early Appear- ances, Diagnosis, and Treatment of Tuberculosis of the Uppei Air Pas- sages," by Chappell. J. Am. Med. Assn., Feb. 21, 1903. Allen: "The Treatment of Cancer by Caustic Taste," N. Y. Med. Record, Dec. 13, 1903. Teissier: "Action anesthesique de I'orthoforme dans le traitcmcnt par I'injestion iodee de I'hydrocele," Eef. : Le Scalpel, 1903, No. 21. Bardet: "Les Intoxications par I'orthoforme, le meilleur mode de prescription de I'orthoforme," Bull. d. la Soc. d: Therap., 1904, No. 9; also, Nouveaux Eemedes, 1904, No. 11, 21. Murdoch: "Further Eemarks on Orthoform in the Diagnosis of Gastric Ulcer," Med. News, 1904, No. 15. Audebert: Trilune med., 1904, No. 40. Tolnai: "Einige pulverformige Antiseptika," Budapesii Orvosi Ujsdg, 1905, No. 11. Baumgarten: "Therapeutische Erfahrungen auf dem Gebiete der Ehinolaryngologie ; Orthoform und Anaesthesin," Budapesii Orvosi Ujsdg, 1905, No. 13. Saxtorph-Stein : "Behandlung der Larynxtuberkulose," Deut. Med.- Zif}., 1906, No. 24. Schroder: "Diagnose und Behandlung des chronischen Magenge- schwUrs," Lancet Clinic, Dec. 15, 190G. Hoffman: "Daueranasthesie im tuberkulosen Kehlkopf," Munch. med. Woch., 1908, No. 14. Limburger: "Uber Lokalanasthesie," Zahnarztliches Centralbl., 1908, No. 4. Orthoform-New Hydrochlorid. — Orthoform-new hydrochlorid (C«H«03N.HC1) is the hydrochlorid of methyl meta-amino-para-oxybenzoate. It is a white, crystalline powder, having an Indefinite melting point and an acid reaction. It is soluble in 10 parts of water. Its reactions are the same as those of Orthoform-New, except that it gives a reaction for chlorids with silver nitrate and has an acid reaction; 3.65 gm. dissolved in 50 c. c. of alcohol require not less than 17.8 c. c. nor more than 18 c. c. of normal solution of sodium hydroxid to produce a neutral liquid. Its in- compatibilities are the same as those of Orthoform-New {q. v.). Actions and Uses. — The actions, uses, and dosage of this compound are similar to those of Orthoform-New (q. v.) ; but it is freely soluble in water. It has been employed hypodermically, but this method of appli- cation is not always satisfactory, for the reason that solutions are in- clined to be somewhat acid and have been known to produce irritation at the site of injection. Orthonal. — The name is given to a local anesthetic intended for dental use. It consists of cocain hydrochlorid, 0.5 gm. ; alypin, 0.75 gm. ; 798 ANESTHESIA adrenalin solution (1 ,to 1,000), 6 gni. ; physiological salt solution, enough to make 100 gm. It is put up in ampules holding 1 to 3 c. e. ; 1 to 3 c. c. are used subcutaneously for anesthesia, according to Schleieh's infiltration or Oberst's method. On Orthonal, see : Barry: Zalindrztl. Rundschau, 19, No. 10; Friedrich: Berlin zahndrztl. Halhmonatsschr., 1911; Sander-Calbe : Zentr. Zalinlieilh., Jf^, No. 8; Brandes: Deut. Monat. Zalinlieilh., 1910, No. 3; Schulze: Zahndrztl. Rundschau, 19, No. 27; Seefeld: Ihid., 19, No. 50; Moses: Deut. med. Woch., 37, No. 46, 2138; Eabow: Ghem.-Ztg., 1912, No. 29, 258 ; Flury : Z. angew. Chem., 26, No. 35, 242. Otis Mixture. — Chloroform, 3 parts; alcohol, 4 parts; and ethyl bromid, 1 part (Miiller: "Narkologie," 1, 492). Otis employed this mixture extensively in general and obstetric surgery. Ouabain. — Ouabain (CjoH^gOia) is a glucosid from the ouabai root, an acocanthacese, and is also found in one of the strophanthus species (Strophanthus gratus). In 1882 Arnaud obtained from an unidentified species of the genus Acocanthera a crystalline glucosid, and, in 1893, Lewin separated from the cocanthera deflersii an amorphous glucosid. Arnaud assigned to ouabain the formula CgoH^gOia- Grley (Compt. rend. Soc. biol., 1895, ii), whose statements have been largely corrobor- ated by Sailer, Lewin, and others, reported that ouabain was a local an- esthetic, having ten times the power of cocain. On ouabain as a local anesthetic, see Panas, "Sur Faction anes- thesique locale da la strophantine et de I'ouabaine," Bull, de VAcad. de Med. de Paris, 1890, No. 7. Strophanthus glaber contains ouabain, which, according to Karsten (Compt. rend., 126, 346), is identical with Strophanthin (q. v.). Oxygen. — Gray (1874) found oxygen to serve as an anesthetic for short operations (see Richmond Med. Mon., June, 1879) ; it is not a true anesthetic, however, Oxysparteinum Hydrochlorid. — The hydrochlorid of oxyspartein, an oxidation product of the alkaloid spartein from Spartium scoparium. It forms white crystals, melting at -|- 48-50° C, and is soluble in water and alcohol. It is used to prevent cardiac disturbances during chloroform narcosis. Pantopon (Omnopon). — The preparation introduced by Sahli (Therap. Monatsh., 1909, No. 1; see, also, Pharm. Centrh., 50, 49), un- der the name "Pantopon," is said to contain the alkaloids of opium in the same proportion in which they occur in nature in opium itself (89.77 per cent alkaloids as hydrochlorids, 50 per cent of which is mor- phin). It is a brownish powder, soluble in water, forming with the lat- ter a brown solution. The alkaloids are comlnned with hydrochloric acid. The variable composition of opium would seem to render it al- A LIST OF ANESTHETICS 799 most impossible to obtain a preparation of uniform composition and of uniform therapeutic action in every case, and further experience is re- quired to enable us to decide on the special indications of pantopon. Sahli stated that it could not be regarded as an exact substitute for morphin; but Eodari (Therap. Monatsh., 1909, 540) came to the con- clusion that the narcotic and hypnotic action observed clinically by Sahli could also be obtained on animals, and that this action determined its chief advantage. The pharmacological studies of Wertheimer-Eaf- falovich (Deut. med. Woch., 1910, No. 37) demonstrate that pantopon has a decided hypnotic action on animals and affects the respiratory cen- ter less than morphin. Similar results were obtained by Loewy aiid Bergien {Miinch. med. Woch., 1910, No. 46), the latter also showing that pantopon had no effect upon the circulation. These characteristics indicated that pantopon would be a suitable substitute for morphin in scopolamin-morphin anesthesia, and Brlistlein (Correspondenz. f. schweizer Aerzte, 1910, No. 26) proposed its use for this purpose. Grafenberg (Deut. med. Wocli., 1910, Nos. 34 and 39) considered that the scopolamin might be omitted. He also tried general anesthesia by means of ethyl ether with pantopon injections alone, and procured very satisfactory results. On the action of pantopon on the digestive canal, see Cohnheim and Modrakowski: Z. pliysiol. Chem., 71, 273. Brlistlein {Corr.-Blatt. f. schweiz. Aerzte, J^O, 826) reported that scopolamin hydrobromid in 75 parts of water and 25 parts of glycerol containing 2 per cent of pantopon made a clear solution which was narcotic. He considered that pantopon was entirely devoid of disturbing substances and side actions. German Patent 229,905, of October 10, 1909, of F. Hoffman-La Eoche & Co., claims a process for the manufacture of preparations containing all the alkaloids of opium in a readily soluble form suitable for subcutaneous injection. An aqueous acid extract of opium is precipitated with alka- lies, the alkaline precipitant, separated from the precipitate, is shaken with organic solvents, the alkaloids are removed by shaking out with acids yielding water-soluble salts, the alkaloids precipitated with alkalies and purified are dissolved in the acid alkaloid solution, and the solution is dried. The products are stated to give the reactions for morphin, nar- cotin, papaverin, and thebain. On morphin-free pantopon, see Winternitz, Miinch. med. Woch., 59, 853. On pantopon anesthesia, see the following : Sahli: Miinch. med. Woch., 1909, No. 26; Therap. Monatsh., 1909, No. 1. Hallervorden : Therap. der Gegenwart, 1910, No. 5, 206. Heimann: Miinch. med. Woch., 1910, No. 7, 357. ' Eodari: Therap. Monatsh., Oct., 1909. 800 ANESTHESIA Gottlieb and v. d. Eeckhart: "Festsclir. f. Schmiedelerg," 1910, 235. Becker: Reiclis-Med.-Anz., 1910, No. 18, 273. Witowski: Arch. f. ex per. Path. u. Pharmakol., 17. Jager: Munch, med. Woch., 1910, 2238. Eaffalovitch : Deut. med. Woch., 1910. Briistlein: Correspondenz. f. schweiz. Aerzte, 1910; Zentr. Chirurg., 1911, No. 10, 345. Ewald : Berl. Min. Woch., 1910, No. 35 ; Munch, med. Woch., 1910, No. 25, 1326. Burgi: Deut. med. Woch., 1910. Sahli: Zentralhl. f. d. gesammte Therapie, 1909; Berl. Min. Woch., 1910, No. 35, 1G09. Griifenberg: Deut. med. Woch., 1910, No. 34, 1569. Doblin: Therap. Monatsh., 1911, 'No. 4, 21C). Leipoldt: Lancet, Feb. 11, 1911, 3.68. Zollinger: Correspondenz. f. schweiz. Aerzte, 1911, No. 10. Eobertson: Lancet, Oct. 7, 1911. Fowelin: Zentr. Chirurg., 1911, No. 27, 921. Hellman: Am. Med., n. s., 7, No. 1, 39. Voigt: Therap. Monatsh., 1911, 601. Haymann: Miinch. med. Woch., 1911, No. 2, 82. In employing omnopon in the induction of anesthesia before opera- tions, Leipoldt found that omnopon injections are more effectual than a combination of Omnopon and Scopolamin (q. v.), since it occasions neither nausea nor vomiting. Krauss: Zentr. Chirurg., 1911, No. 20. Zahradnicky: Ibid., 1911, No. 30, 1017. Aulhorn: Miinch. med. Woch., 1911, No. 12, 618. Johannsen: Zentr. Gyndk., 1911, No. 19, 702. Zeller: Miinch. med. Woch., 1911, No. 25, 1355. Kolde: 75iU, 1911, No. 28, 1499. . Simon: 76td, 1911, No. 32, 1725. Dornbliith: Deut. med. Woch., 1911, No. 15, 697. Kafemann: Med. Klin., 1911, No. 26, 1002. Heinsius: Berl. klin. Woch., 1911, No. 41, 1837. Anneler: Arch. Fliarm., 250, 186. Mannich and Schwedes: Apoth.-Ztg., 2S, 82. For other preparations containing the alkaloids of opium, see Isopon, Nealpon, Opiopon, Opon, and Summopon. Paraldehyd. — This compound was found to act similarly to chloral, but caused deep sleep and no convulsive movements. (See Archiv f. exper. Pathol, u. Pharmakol., 1882.) Noto {New Orleans Med. and Chir. J., 1900, No. 9) believed that paraldehyd was a remedy which, when administered internally in hypnotic doses of 2 to 3 gm., 30 minutes A LIRT OF ANESTHETICS 801 to one hour previous to narcotization l)y cliloroform, completely divested the latter of its attending dangers. 'I'he ancstlietic properties of paralde- hyd are more marked than those of acetaidehyd ; it is less toxic than me- taldehyd. It acts first on the higher cerebral centers and then oji the other parts of the central nervous system, finally causing spinal anes- thesia and death. It is said to have no depressant action on the licart. However, it possesses a very unpleasant odor and taste, and has an ir- ritant action on the gastric mucosa (Francis and Fortescue-Brickdalo: "The Chemical Basis of Pharmacology,^' 1908, 107-8). On employment of paraldehyd in intravenous anesthesia, see, also: Lancet, Sept. 21, 1913, 818; Nov. 2, 1912, 1220. Para-amidobenzoic Acid Ethyl Ester. — A white powder, melting at -f- 90-91° C, and possessing the following composition: NH2.CoH,.COOC2l-I,. It is used as a local anesthetic. Para-amidobenzoic Acid Isobutyl Ester. — Soft, colorless needles, m.elting at -|-"65° C, possessing anesthetic properties. Paraneplirin. — An extract from the suprarenal glands which is free from albumoses and peptones. In dental practice it is employed in com- bination with tropacocain; see, also, combinations which follow {infra). Paranephrin-cocain Mixture. — A dental anesthetic consisting of paraneplirin 1: 1,000 and 1 per cent of cocain. Paranephrin-cocain-subcutin. — A hemostatic local anesthetic for sur- gical and dental jDractice. Paranephrin-novo-subcutin. — This preparation contains novocain, and is employed as a general as well as a local anesthetic, especially in dental surgery. Pate de Vide. — Bonbons containing aconitin, heroin, and stovain. Pental (Trimethylethylene; beta-isoamylene). — Pental [(0113)20 = OH'.OH,] is an anesthetic which has beeiL used in minor surgical cases, as tooth extraction; but it possesses toxic properties, and hence is not favored. Pental was highly recommended by W. Lombardino as an anesthetic of great practical value. Wood and Oerna have shown, how- ever, that it acts on lower animals as a powerful cardiac depressant, and is probably a dangerous anesthetic. That it possesses real danger is shown in the statistics gathered by Gurlt, who recorded that there were 6 deaths in 600 pental narcoses; and, moreover, Kleindienst found that very frequently in man severe albuminuria results and that not infre- quently hematuria and hemoglobinuria occur three or four days after pental narcoses. On the employment of pental, see the following: Breuer and Lindner : "Ueber Pentalnarkosen'' ; v. Hacker's "Ohir. Beitr. a. d. Erzherzogin-Sophien-Spital," Vienna, 1892; Zentr. Chir.^ 1893,91.- 802 ANESTHESIA Gurlt : "Zur Narkotisierungsstatistik/' Verh. d. XXVI. Deut. Chirur- genhongr., 1897, Teil ii, 202. Hollander: Therap. Monatsli., 1891 and 1892; Deut. med. Woch., 1892, 757; J. f. Zahnheillc., 1893; Zentr. Cliir., 1893, 517. Kleinschmidt : "Ueber Pental als Anasthetikum," Deut. Z. f. CJiir., 35, 333. , Philipp: "Ueber Pentalnarkose in der Chirurgie," Yerh. d. XXL Deut. Chirurgenhongr., 1892, Teil ii, 367. Van Eeysschoot: "Contribution a I'etude experimentale du pental," Gand, 1892. Eieth : "Ueber die Pentalnarkose," v. Brims' Beitr., 1893, 10, 189. Von Rogner: "Das Pental in der chirurgischen Praxis," Wiener med. Presse, 1891, No. 51; Zentr. Cliir., 1892, 93. Weber: "Pental, ein nenes Anasthetikum," Dissertation, Halle, 1891 ; Miincli. med. Woch., 1892, No. 7. Pentane (Amyl Hydrid). — A liquid hydrocarbon from naphtha, pro- posed as an anesthetic. See Hydramyl. Pentylene. — See Hydramyl. Peronin. — This morphin derivative, benzyl-morphin hydrochlorid [Ci^HigNOa.O.CeHg.CHg.HCl] has been shown to act as a local anes- thetic for the eye. Buffalini (Settimana med., 1899, No. 27) found that the instillation of a few drops of a luke-warm 1 to 2 per cent solu- tion of peronin into the conjunctival sac induced complete and deep an- esthesia of the cornea enduring for many hours. Guaita {Hid., 1899, No. 40) confirmed the statements of Buffalini. On Peronin as a local anesthetic, see the following literature: Buffalini: "La Peronina, nuovo anestesico locale," Settimana med., 1899, No. 27; Virchow-Hirsch's Jahresber., 1899, 1, 393. Guaita: "Sopra I'azione anestetica locale della peronina," Ann. di Farm.acoierap., 1899, No. 9, 10. Pierard: "Quelques experiences sur Paction physiologique de la Peronine," Ann. de la Soc. des Sci. med. de Bruxelles, 1899, No. 8. Phenol. — See Carbolic Acid. Phenol Camphor. — See Camphor, Phenylated. Phenolcocain. — See Cocainum Phenylicum. Phenyl-urethane. — This compound, also known as euphorin, has the following formula: /OCH26 CO \ ^NH.CsHb It forms colorless, crystalline needles, melting at + 49°-50° C, and dissolving in alcohol and ethyl ether. Stroll (Miinch. med. Woch., 1907, A LIST OF ANESTHETICS 803 No. 45, 2262) drew attention to the use of phenyl-urethane in the treat- ment of painful ulcers of the foot ; in his experience the preparation was superior in anesthetic power even to anesthesin and orthoforra. Phenjrphrin. — A dental local anesthetic containing, per c. c. of physi- ological salt solution, 0.02 gm. alypin and 0.1 gm. "Nebennierenextrak- losung" (1:1,000). Phcenixin. — Carbon Tetrachlorid (q.v.). Plecavol. — A tooth cement. A flask with plevacol powder : Para- amidobenzoyleugenol, eugenol, zinc oxid, zinc sulphate, and gum arabic. A flask containing a solution of tricresol-formalin is also required. An- esthetic and antiseptic acting pulpa-capping material and fllling material for roots, used in dentistry. It is said to act without irritation, conserv- ing the pulpa, and hardening in a short time. Pleistopon. — Narcotin-free Pantopon (q. v.). Polychloral. — This is obtained by adding pyridin, drop by drop, to chloral, washing out the resulting solid with dilute hydrochloric acid and then drying. It dissolves slowly in water, more quickly in alcohol, form- ing chloral hydrate and chloral alcoholate respectively. An anesthetic and hypnotic. Polychlorated Hydrochloric Ether. — See Ethyl Chlorid Polychlo- rated. Potassocain or Pottasocain, — This contains cocain dissolved in alcohol and ether. Propesin (Propasin). — A German local anesthetic; it is the propyl ester of paramido-benzoic acid, NH2<^ \cOOC3H7. It is a white crystalline powder which melts at + 73-74° C. It is readily soluble in alcohol, ether, and chloroform, but dissolves with difficulty in water. Said to be practically nontoxic, and to act very promptly and effectively on mucous membranes. On propesin, see the following: Kluge: Therap. Monatsli., Feb., 1909, 77. Stiirmer and Liiders: Deut. med. Woch., 1908, No. 53, 2310. Dietrich : Deut. zahndrztlichen Ztg., 1910, No. 16. Perl: Med. Klinilc, 1909, No. 50, 1892. On the use of propesin in urology and gynecology, see Medizin. Klinih, 1908, 1769, Kluge states that the only disadvantage of propesin is that its slight solubility in water renders it unsuitable for subcutaneous injection. Propesin-colloid contains, according to Pliarni. Ztg., 55, 858, 20 per cent propesin, 72.5 per cent glycerin, 2.5 per cent starch, and 5 per cent ethyl alcohol. On propesinol, see linger: Apoth.-Ztg., 27, 1023. See Dipropesin. 804 ANESTHESIA Propion. — Diethyl ketone (C2H5.CO.C2H5), also known as metace- tone, propione, and ethylpropionyl, is a colorless, mobile liquid, posses- sing an acetone odor; it boils at + 101° C. Propion was recommended as a hypnotizing agent by Albanese and Barabini {Ann. di chem. e farmaeol., Feb., 1893, 124; April, 1892, 225), who observed that it caused, when administered to dogs and rabbits in doses of 1.0 to 1.5 gm., deep, tranquil, and enduring sleep, the compound being readily absorbed when introduced into the stomach or rectum, or when injected in sub- cutaneous tissue. The inhalation of diethyl ketone also induced sleep, but this property did not seem to be of any practical value, since, in this method of application, the narcosis was effected too slowly. See, also, Noera: Arch, di farmacol. e terap., 1896, 4, f. ii, 12. The solubility of propion in water is not great and, in addition, its taste is impleasant. Puff-Bali. — In 1853, Eichardson, having learned that the "smoke" (cloud of brov/n dust-like spores) of that curious fungus, the common puff-ball, had been used by country folk for the stupefaction of bees, conceived the idea that it might be used as a general anesthetic. He conducted experiments upon dogs, cats, and rabbits, and in one case re- moved a tumor from a dog without observing any indications of pain during the operation {Med. Times and Gaz., 1853, 610). To quote Lyman ("Artificial Anesthesia and Anesthetics," 1881, 328), when a moderate quantity of the smoke was gradually inhaled, anesthesia ap- peared and disappeared slowly. The animal exhibited all of the symp- toms of intoxication, accompanied by convulsions and sometimes by vomiting. Life ceased by degrees; after the induction of complete in- sensibility, a dog might inhale the smoke for twenty minutes or even half an hour before death resulted. Bespiration always ceased before the action of the heart. Herapath made experiments which proved that the active agent in producing the preceding phenomena was carbon di- oxid, generated during combustion; his conclusion, confirmed by Snow, was accepted by Eichardson. It would seem from these experiments {Phil. Mag., July, 1855) that the anesthetic effects are not owing to a narcotic. See Carl)on Dioxid. Pyridin. — This is a liquid of a powerful odor, the vapor of which, if inhaled, stimulates the fifth nerve and produces dyspnea, then slow, shallow breathing, and finally sleep. In very large doses it paralyzes the sensorium, producing complete anesthesia and abolition of reflexes; smaller doses may inhibit respiration. Piperidin and pyrollidin have much the same action (Prancis and Portescue-Brickdale's "The Chemical Basis of Pharmacology," 1908, 250). Pyrocain. — A guaiacol-benzyl ester, said to be a nontoxic local anes- thetic. Pyrrol (Pyrrhol). — Pyrrol was experimented with by the Committee of the British Medical Association. In the frog it produced anesthesia A LIST OF ANESTHETICS 805 with considerably less rapidity than chloroform, and great excitement and muscular spasms preceded complete anesthesia. Its hypodermatic administration to three young rabbits produced spasmodic movements, principally involving the jaws and fore-paws; these rabbits were not decidedly anesthetized. ftuinin Alkaloids. — Morgenroth and Ginsberg (Berl. Jclin. Woch., 50, No. 8) investigated the effect of the quinin alkaloids upon the cor- nea. The compounds studied combine with ethylhydrocuprein to form isopropyl, isobutyl, and isoamyl hydrocuprein. A 3 per cent solution of quinin hydrochlorid and 1.0 to 1.25 per cent solutions of hydroquinin and ethylhydrocuprein hydrochlorid produced complete anesthesia of the cornea; with the transformation of the ethyl to the propyl compound, a marked increase in anesthetic action resulted, for with isoaraylhydro- cuprein a 0.1 to 0.125 per cent solution was sufficient. Isoamylhydro- cuprein proved to be at least 20 to 25 times more active than cocain. Quinin and Urea Hydrochlorid (Quininge et Urese Hydrochloridum ; Chininum bihydrochloricum Carbamidum). — Quinin and urea hydro- chlorid (C2oH2iK202.HCl + Cri4N20.HCl+ 5HoO) is a compound of quinin hydrochlorid and urea hydrochlorid containing approximately GO per cent of anhydrous quinin. The preparation is made by dissolving 400 parts quinin hydrochlorid in 300 parts of dilute hydrochloric acid, sp. gr. 1.061, mixing the solution with 60 to 61 parts of pure urea [C0(NH2)2], warming the mixture until dissolved, filtering it through glass wool and setting the filtrate aside for crystallization. After twenty- four hours the crystals are brought on a filter, drained, washed with very cold distilled water, spread on flat plates and dried at room tem- perature. The mother-liquor is evaporated and again set aside for crystallization. The second mother-liquid, which is colored brown, is exposed in a dish to spontaneous evaporation, during which all of the double salt of quinin slowly crystallizes out and may be separated. The hydrochlorid of quinin and urea crystallizes from hot solutions in hard, white, interlaced four-sided prisms. On spontaneous evapora- tion of a concentrated solution, very large transparent prisms are found. The salt dissolves at ordinary temperature in its own weight of water, forming a somewhat viscid straw-colored liquid, not altered by exposure to light. During its solution a marked lowering of temperature occurs. It is not hygroscopic and is unalterable in the air, excepting that when warmed the crystals lose their transparency and become yellowish. They fuse at from 70° to 75° C. (158° to 167° F.) with the loss of 10 per cent of water, forming a yellowish liquid which congeals, on cooling, to a yellow mass. If this mass is allowed to stand in the air, it takes up water, after a few days, equal in amount to that expelled, and again be- comes white. If the melted salt is dissolved in water, it may be com- pletely recovered in a crystalline form. It is also soluble in alcohol, and 806 ANESTHESIA from this solution a salt of somewhat variable composition is precipitated by ether. It is soluble in about 800 parts of chloroform. Its water solu- tions are of a strong acid reaction. A solution of the salt in water (1 to 20) shows no fluorescence; but if one drop of this solution is added to 10 c. c. of distilled water in a test tube, a vivid blue fluorescence is developed." On drying the salt at -(- 125° C. to constant weight and cool- ing in a desiccator, it should not lose more than 16.5 per cent of its weight (corresponding to five molecules of water of crystallization). On ignition, the pure salt is slowly consumed, leaving no residue. Am- monia water, alkaline hydroxids or alkali carbonates throw down from the water solution of quinin and urea hydrochlorid a white precipitate of alkaloidal quinin, which, when carefully washed with cold distilled water until free from chlorids, and dried at a low temperature, should conform to the reactions and tests given in the United States Pharma- copoeia under quinin. One gram dissolved in 2 c. c. of distilled water, and well shaken in a stoppered test-tube with 6 c. c. of ether and 2 c. c. of 10 per cent ammonia water, should be dissolved completely, and no crystals should separate out from the ethereal solution on standing for six hours. If the ethereal stratum is removed to a tared beaker, and the contents of the test-tube are washed successively with three portions of 5 c. c. each of ether and these ether washings be also added to the tared beaker, the alkaloidal quinin remaining after evaporating off the ether, dried at -f- 125° C. to constant weight, shovild weigh not less than 0.592 gm. On the chemical and physical properties of Quinin and Urea Hydrochlorid, see Schaefer: The Drug. Cir., Feb., 1910. Actions and Uses. — Quinin and urea hydrochlorid has the actions of quinin. It is non-irritating when injected hypodermically. Eecent in- vestigations have shown that, when injected hypodermically or when ap- plied locally to mucous membranes, it exerts an anesthetic action similar to that of cocain. It is reported that the anesthesia is in some cases prolonged for several days. Sylvester, of Wellston, Ohio, is reported as having employed quinin for more than twenty years as an anesthetic to denuded and mucous surfaces, but not hypodermically. In July, 1896, before the Chautauqua County, N. Y., Medical Society, Griswold reported on its hypodermic use as an efficient local anesthetic. It was Henry Thibault who found that quinin and urea hydrochlorid, employed ex- tensively in the South for the hypodermic treatment of malaria, rendered the site of the injection anesthetic for a considerable period. He experi- mented further and learned that 1 to 2 per cent solutions produced local anesthesia which lasted from 1 to 6 hours and proved to be safer than cocain. On the use of the preparation in various operations, consult the fol- lowing : Hertzler, Brewster, and Eogers: J. Am. Med. Assn., Oct. 23, 1909, A LIST OF ANESTHETICS 807 1393; The Prescriher, 1910, 19; Klin.-Uierap. WocUenschrifl, 1910, 96. MacCampbell : J. Am. Med. Assn., May 14, 1910. Hertzler: Ibid., April 23, 1910, 1375; and June 11, 1910, 1940. Hirschman: Lancet-Clinic, July 9, 1910. Med. Council, April, 1910, IIG; May, 1910. Green: J. Am. Med. Assn., June 11, 1910. Merck's "Eeport," Nov., 1911, 356. Ellis: Therap. Notes, January, 1912, 7. These contributions show that subcutaneous injections of a 1 to 2 per cent solution of quinin hydrochloro-carbamid and the local application of a 10 to 20 per cent solution occasionally have a better anesthetic action than cocain. See Ghevannes Local Anesthetic. Dosage. — The same as quinin. For the production of local anes- thesia, injections of a solution of from ^ to 1 per cent strength are used. The i^ per cent solution is said to be free from the risk of pro- ducing fibrous indurations, which sometimes occur with the stronger solution. For application to mucous membranes solutions varying in strength from 10 to 20 per cent should be used. Radestock's Mixture. — An anesthetic mixture of chloroform, 2 parts, and ethyl ether, 3 parts (Miiller, "Narkologie," 1, 493). Radikal-Anasthetikum Apotheker Maier. — A solution containing co- cain, phenol, iodin, and pyrazolin. Radinin. — A preparation insensitive to light and air ; it will keep in a 1 per cent cocain solution without adrenalin. Rapid Respiration, Anesthesia by. — Bonwill and Hewson called at- tention to a form of insensibility to pain induced by rapid respiration, and the matter was discussed by the Philadelphia County Medical So- ciety {Med. Rec, Aug. 21, 1880). Bonwill and Lee reported that the best method of producing this kind of analgesia was by causing the patient to lie upon the side, with a handkerchief over the eyes in order to avoid distraction of the attention. He was then directed to breathe about one hundred times per minute, expelling the air by a succession of puffing expirations. After from two to five minutes of this exercise, there was developed a degree of insensibility to pain which persisted for as long as thirty seconds. The movements of the heart were accelerated and the force of the pulse was diminished. Consciousness and the sense of touch were not abolished. After the production of this condition, a smaller quantity than usual of the ordinary anesthetics Avere required to produce complete insensibility. For a discussion of this method, see Lyman : Loc. cit. For a consideration of superventilation by means of oxygen, see Chapter 11. Reichel's Zahnschmerzstillende Tropf en. — A Japanese peppermint oil free from menthol, also known as "Poho Oil." 808 ANESTHESIA Renocain. — An adrenalin solution containing cocain, intended for use as a local anesthetic. Renoform. — The active principle of the suprarenal gland. It is a white, crystalline powder, difficultly soluble in cold water, easily soluble in acidified water; used in operations for localizing anesthetics, in com- bination therewith. Rhigolene. — A petroleum ether of low boiling point. Ehigolene was introduced by Bigelow in 18C6. See JEtlier Anwstheticus (Koenig). Rhinosol. — A hay-fever remedy containing Anesthesin (q. v.) and paranephrin. Richardson's Methylen Chlorid. — A mixture of chloroform and methyl alcohol. Richardson's Mixture. — Chloroform, 2 parts; alcohol, 2 parts; and ethyl ether, 3 parts (Mliller, "JSTarkologie," 1, 492). Eichardson (Sci. Am. SuppL, No. 51G, 8240) said, in reference to the varying proportions of alcohol, chloroform, and etlier used by different administrators in compounding A. C. E. Mixture, that he thought that 4 parts ether, 2 parts chloroform, and 2 parts alcohol, by fluid measure, were the best proportions, and that it was "altogether a very good mixture." Robiol. — Eobiol and Novorobiol are combinations of suprarenin with local anesthetics (Flury: Z. angeiu. Chem., 26, 242). Royal Medical and Chimrgical Society Committee Mixture. — Alcohol (sp. gr., 0.838), 1 part; chloroform (sp. gr., 1.497), 2 parts; ether (sp. gr., 0.735), 3 parts (Hewitt: "Anesthetics and Their Administra- tion," 3rd ed., 406). Sal Anaestheticum Schleichii. — A varying mixture of cocain hydro- chlorid, morphin hydrochlorid, and sodium chlorid, to induce anesthesia by infiltration according to the method of Schleich. In 1894 Schleich ("Schmerzlose Operationen,"'- Berlin, 1894) first propounded the doc- trine of anesthesia by artificial edematization of the tissues by means of morphin-cocain injection. A number of papers were subsequently pub- lished on the practical aspects of the subject : Krecke : Munch, med. Wocli., 1897, No. 42; Eeichold: lUd., 1167; Briegleb : Therap. Monatsh., 1897, No. 12, 651; Haberern: Ungar. med. Presse, 1897, No. 46, 1094; Simon-Cohn: Berl, klin. ^¥ocll., 1897, No. 30. The anesthetizing mixture originally proposed by Schleich was of three different degrees of strength, namely: 1. Sal ansestheticum Schleichii I (strong): Cocain Hydrochlorid 0.2 (gr. 3) ; Morphin Hydrochlorid .025 (gr. 1/3) ; Sodium Chlorid 0.2 (gr. 3). 2. Sal ansestheticum Schleichii II (normal) : Cocain Hydrochlorid 0.1 (gr. 1 2/3) ; Morphin Hydrochlorid 0.025 (gr. 1/3); Sodium Chlorid 0.2 (gr. 3). A LIST OF ANESTHETICS 809 3. Sal anaestheticum Schleichii III (weak) : Cocain Hydrochloric! 0.01 (gr. 1/6) ; Morphin Hydrochloric! 0.005 (gr. 1/12); Sodium Chlorid 0.2 (gr. 3). Each of the three mixed powders was dissolved shortly before use in 100 c. c. of boiled distilled water, and these solutions were directed to be used only when cold, since otherwise their anesthetic properties were lost. It was known in 1897 that cocain could be suitably replaced by Tropacocain {q. v.). Ethyl chlorid was usually employed as a pre- cursor of infiltration anesthesia. In 1898 Custer [Munch, med. Woch., 1898, ISTo. 22) showed that tropacocain was decideclly preferable to co- cain, especially when required for Schleich's infiltration method. The solutions required for infiltration were stated to be of the same degree of concentration as cocain hydrochlorid, i. e., 0.2 per cent in the case of solution I; 0.1 per cent in that of solution II; and 0.01 per cent in the case of solution III, which was found to act as an "ancestheticum doloro- sum." For further details, Custer's paper should be consulted. In 1901 Schleich (Deut. Klinih, 1901, parts 22 and 23) recommended exclu- sively one of the three infiltration fluids originally formulated by him, namely, the normal solution II, which might, according to the require- ments of the case, be intensified by the addition of tropacocain or weak- ened by that of a sterilized 0.2 per cent solution of sodium chlorid. In 1906 Schleich ("Schmerzlose Operationen," 5th ed.; Allg. med. Zen- tral-Ztg., 1906, JSTo. 48, 872) reported that he had found it of advantage, in his method of producing anesthesia, to use a combination of cocain with Alypin (q. v.), since a greater effect was obtained in this manner. He consequently advised the substitution for the older solutions of the following : I II III Cocain Hydrochloride 0.1 0.05 0.01 Alypin 0.1 0.05 O.Oi Sodium Chlorid 0.2 0.2 0.2 Distilled Water 100.0 100.0 100.0 He avoided the addition of adrenalin for fear of unpleasant sec- ondary effects. Salolcamphor (Salolum Camphoratum) . — A mixture of 3 parts of salol and 2 parts of camphor. A local antiseptic and anesthetic. Sanoform-Preparations. — Sanoform-cocainol-streupulver contains 10 per cent of sanoform (diiodosalicylic acid methyl ester) and 10 per cent of Ancesthesin (q. v.). Sanovagin. — See Cocainol-Crenie. Sansom's A. C. Mixture. — Alcohol, 1 part by volume; and chloroform, 1 part by volume. See Med. Times and Gaz., 1870, 2, 107. Sansom found that alcohol "had the greatest effect in sustaining the heart's action 810 ANESTHESIA during the influence of chloroform." He found it impossible to kill with chloroform a frog which had previously inhaled the vapor of alco- hol. In the opinion of Sansom, if chloroform is to be used without an inhaling apparatus, in order to insure a supposed uniformity of strength of vapor, it, should be mixed with alcohol, or with alcohol and ethyl ether. Schafer and Scharlieb's A. C. Mixture. — A mixture of absolute alco- hol, 1 part by volume, and chloroform, 9 parts by volume. See Trans. Roy. Soc. Ednh., Jfl, part ii, No. 12. Schleich's Anesthetics. — Owing to their low boiling points, these mixtures are said to be rapidly eliminated from the system. (1) Chloroform, 45 parts; petroleum ether ( -f- 60° C), 15 parts; ether, 180 parts; boils at 4" 38° C. (2) Chloroform, 4 parts; petroleum ether, 15 parts; ether, 150 parts; boils at + 40° C. (3) Chloroform, 30 parts; petroleum ether, 15 parts; ether, 80 parts; boils at -|- 42° C. Mixture 1 is used in short operations, while 2 and 3 are for major periods. For a full discussion of Schleich's Anesthetic Mixtures, see Meyer: J. Am. Med. Assn., Feb. 28, 1903 ; and Med. Rec, Aug. 15, 1908. See Anesiliol. Schleich's narcotic mixture contains 2 parts of ethyl chlorid, 4 parts of chloroform, and 12 parts of ethyl ether. It is said to sup- press local pains with rapidity and certainty. See Schleich: Therap. der Gegenwart, March, 1902. Cf. Sal Ancestheticum Schleichii. Scopolamin Hydrobromid. — Scopolamin hydrobromid ( Scopolamina? hydrobromidum) is the hydrobromid (Ci,H2i]Sr04HBr.3H20) of an al- kaloid obtained from plants of the Solanacece ; it is chemically identical with hyoscin hydrobromid U. S. P. According to the British Pharma- copoeia, it is "the hydrobromid (C17H21NO4.HBr.3H2O) of an alkaloid contained in hyoscyamus leaves, different species of scopola, and possibly other solanaceous plants." Hyoscin hydrobromid was introduced in the United States Pharma- copoeia in 1890. Hyoscin (C17H21NO4) is found in the leaves and seeds of Hyoscyamus niger, Duboisia myropoides, Scopola japonica, Atropa bel- ladonna, and other solanaceous plants; it forms, when pure, a sirupy liquid. The hydrobromid forms colorless, transparent, rhombic crystals, odorless, possessing an acrid, slightly bitter taste, and slightly efflorescent. It is soluble in 1.5 parts of water, 16 parts of alcohol, and in 750 parts of chloroform at -|- 25° C; it is insoluble in ethyl ether. The water solu- tion shows a slightly acid reaction to blue litmus paper. When hyoscin hydrobromid is heated, it softens at about -|- 100° C; it first fuses and then loses its water of crystallization at -|- 110° C. When dried over sulphuric acid until it is completely deprived of its water of crystalliza- tion, it melts at from -\- 191°-192° C. When ignited, it leaves no resi- due. Schmidt (Pharm. Ztg., 1891, 522) considered that the hyoscin A LIST OF ANESTHETICS 811 hydrobromid of commerce was essentially seopolamin hydrobromid, and Hesse {Ann., 1893, 304) confirmed this view. The United States Phar- macopoeia introduced, in the Eighth Eevision, Scopolaminse hydrobromi- dum production as a separate title, but referred to Hyoscina; hydro- bromidum for the description and tests ; it considered them to be identi- cal compounds. Schneiderlin (Aerztl. Mittheilg. aus und f. Baden, 1900, No. 10) rec- ommended operations under anesthesia by morphia-scopolamin, which method consisted essentially in administering to the patients subcuta- neously, 1^2 to 2 hours previous to the operation, seopolamin and morphia separately, which induce deep anesthesia. Korff {Munch, med. Woch., 1901, No. 29; 1902, No. 27) ; Bios {Burns' Beit. z. Tclin. Chir., 35, No. 3, 565) ; and von Steinbiichel {Centralh. f. Gynakol., 1902, No. 48) sup- plied most favorable reports on the anesthesia obtained in this manner; but Shicklberger {Wien. Min. Woch., 1902, No. 51) maintained that the morphia-scopolamin method was adapted only for those cases which rendered a general anesthesia absolutely requisite and where at the same time chloroform or ether were contraindicated. The Schneiderlin-Korff method of anesthesia by morphia and seopolamin is based upon the fact that the hypnotic and anesthetic properties of morphia and seopolamin associate themselves, while their toxic effects on the respiration and cir- culation, being antagonistic, counterbalance each other. On this method of anesthesia, see the following additional contribu- tions : Grevsen: Miinch. med. Woch., 1903, No. 32, 1383. Bloch: Hid., 1903, No. 26, 1135. Volkmann: Deut. med. Woch., 1903, No. 51, 967. Heinatz: Russkiy chir. Archiv, 1902, No. 6. These authors appeared to be satisfied with the method; in fact, the first three regarded it with favor. Korff: Miinch. med. Woch., 1903, No. 46, 2005. Stolz: Wiener Min. Woch., 1903, No. 41. Stolz ascribed the tranquil nature of the anesthesia to morphia rather than to seopolamin, and considered that it was procurable more perfectly and with less danger by an injection of morphia or of morphia-atropin before the administration of the ordinary anesthetic. Wild: Berl. Min. Woch., 1903, No. 9, 188. Flatau: Miinch. med. Woch., 1903, No. 28, 1198. These two authors regarded the morphia-scopolamin method of an- esthesia as risky and cautioned against its application. Hartog: Ibid., 1903, No. 46, 2003. Hartog found that the combination of the morphia-scopolamin and ethyl-ether methods of anesthesia was free from danger and thoroughly reliable. See, also, Eobertson : Sem. med., 1903, No. 26, 220. 812 ANESTHESIA Schneiderlin : Munch, med. Woch.,, 1903, No. 9, 371. Biimke : Monats. f. Psych, u. Neurol., 1903, 62. Koclimann : Archives internationalcs de pltarmacod. et de tJierap., 1903, 99. Liepelt: Berl. Uin. ^Yoch., 1901, No. 15, 387. Eose: Brit. Med. J., 1903, No. 2242, 1589. Korff: Berl. Idln. Wocli., 1904, No. 33, 882. Wiesinger: Deut. med. Wocli., 1904, No. 36, 1335. Wiesinger considered that the method possessed important advantages and certainly appreciated it. Bonheim: Wiener hlin.-therap. Woch., 1904, No. 11, 329. Bonheim recommended the combination of the anesthesia by scopolamin and mor- phin with the administration of chloroform. Cf. Korff: loc. cit. Landau: Deut. med. ^Yoch., 1905, No. 28, 1108. Eys: Csasopis leharuv ceslcy, 1905, No. 18. Lasek: Ibid., No. 2. Menod: Presse me^.^ 1905, No. 60. The last four authors recorded failures with the method. Kochmann: Milnch. med. Woch., 1905, No. 17. Wartapetian: Aerztl. Rundschau, 1905, No. 17, 202. According to these two authors, the method unquestionably possessed advantages, yet its imj^rovement was necessary. Zahradnicky: Wiener med. Ztg., 1905, No. 5, 65. Stein: Deut. med. Ztg., 1905, No. 29, 313. Eoith: Miinch. med. Woch., 1905, No. 46, 2213. Eotter : Deut. med. Ztg., 1905, No. 2, 21. Wiesinger: Deut. med. Woch., 1905, No. 38, 1525. Defontaine: Sem. med., 1905, No. 29, 345. Puschnig: Wiener hlin. Woch., 1905, No. 16. Eies: Ann. of Surg., Ji.2, 193. Stien: Hospitalstidend^, 1904, No. 43. Terrier and Desjardin : Fresse med., 1905, No. 18. Ziffer: Monats. f. Gehurtshilfe u. Gyndlc, 1905, No. 1. Seelig : St. Louis Med. Rev., Aug. 12, 1905. Eochard: Merch's Arch., 1905, No. 6, 187. Dirk: Deut. med. Ztg., 190b, No. 2, 21. Weingarten : Dissertation, Giessen, 1904. The last twelve mentioned authors recognized the value of the method. Gauss: Miinch. med. Woch., 1905, No. 41, 1998. Kronig: Hid., 1905, No. 52, 2536. Korff: lUd., 1905, No. 52, 2539. Eoussy: Revue neural., 1905, 644. Laurendeau: Presse med., 1905, No. 93, 749. A LIST OF ANESTHETICS 813 Cremer: Textbook on "Painless Confinements"; also Welmans: Pharm.-Zig., 1906, No. 2, 17. Eoith {loc. cit.), to simplify the application of scopolamin, recom- mended the introduction of scopolamin tablets; but Laurendeau and Cremer stated their emphatic opposition to the nsc of tablets in connec- tion with subcutaneous injections. Kionka: Therap. der Gegenwart, 1908, No. 8. Kreuter : Milncli. med. Woch., 1907, No. 9. Bass: Ibid., 1907, No. 11. Hocheisen: Ibid., 1907, No. 11. Holzbach: Ibid., 1907, No. 25. Kortf: Bed. Jclin. Wocli., 1906, No. 51. Janson: Psycli.-neurolog. Woch., 1907, No. 25. Klein: Zentr. f. Gyndhol., 1907, No. 27. Hirsch: Wiener klin. Rundschau, 1907, No. 52. Mansfeld: Wiener Jclin. Woch., 1908, No. 1. Doucet: Gaz. med. de Nantes, 1907, No. 2. Ebert: The Military Surgeon, May, 1907. StefEen: Archiv f. Gynakol., 1907, No. 2. Cazin: 8em. med., 1907, No. 42. Segelken: Klin. Monats. f. Augenheillc., 1907, 75. Eochard: Bull. Gen. de Therap., 1907, No. 15. With the exception of Steffen and Eochard, all the last mentioned sixteen authors give, as a result of their experience, a favorable opinion of the value of scopolamin anesthesia. It may therefore be assumed with Kionka that failures are attributable to the use of impure prepara- tions, of faulty method, or of applying the method to patients who are too feeble. Klein, who studied scopolamin sleep and spinal anesthesia, by themselves and in combination, in gynecological operations, held this view; he reported that scopolamin anesthesia in combination with spinal anesthesia was especially indicated when anesthesia by inhala- tion was contraindicated. Bass stated that "The pain of delivery was considerably reduced in a large majority of the cases (he made observations on more than 100 confinements) by the scopolamin-morphin injections." Kreuter described the value of scopolamin-morphin-chloroform anesthesia as used in more than 100 operations. Baisch : Berl. Jclin. Woch., 1907, No. 11. Moore: La7icet, 1907, No. 4364, 1084. Lindenstein: Miinch. med. Woch., 1908, 2064. The experience of Lindenstein extended to some 150 curgical cases. He recommended the use of solutions Avhich were as fresh as possible, and he ascribed the want of uniformity of action to individual differ- ences. 814 ANESTHESIA Caro : Berl. Tclin. Wocli., 1908, 246. Caro advised that scopolamin-morphin anesthesia be used only in persons whose heart is found to be sound. Martin: Wurttemherg. nied. Korrespond., 1908, No. 50. Boesch: Zentralhl. f. GyndJcol, 1908, No. 49. Hotz: Deut. med. Woch., 1908, 534. Gminder: Beitr. z. Gehurts. und Gyndhol., 1908, No. 2. Kronig: Deut. med. Wocli., 1908, No. 23. Mayer: Zentr. f. Gynakol., 1908, No. 21. Keyserlingk: Petersburger med. Wocli. ^ 1908, No. 21. Bruck: Allg. med. Zentral-Ztg., 1908, No. 44. Kleinertz : Zentralhl. f. Gynakol, 1908, No. 42. Veit: Therap. Mojiatsh., 1908, 1^0. 12. Zuntz: Deut. Aerzte-Ztg., 1908, No. 4. The last eight mentioned authors published communications on the production of scopolamin-morphin partial anesthesia ('"Dammerschlaf") in gynecological practice; they were almost all in favor of the method. Some of them thought that its use should be limited to clinical cases, while Veit thought that it should be limited to urgent cases and only used in neurasthenic women. Compare, however, the extensive experi- ence of Kronig. Nicholson : J. Am. Med. Assn., 1909, No. 14. Nicholson studied the harmful effects from the use of scopolamin. In his opinion, no fatal case had been described in the literature which could be definitely proved to be due to the use of scopolamin. Nichol- son employed scopolamin injections in 650 cases, and found their excel- lent effect and their well known advantages fully manifested in 94 per cent of the cases. Blisnianski: Zentr. f. Gynakol., 1909, No. 9. Schoemaker: Deut. med. Woch., 1909, No. 7. This author used scopolamin-morphin-ether-chloroform anesthesia in 3,000 cases, being well satisfied with the results; no by-effects were pro- duced on the patient. Trancu-Eainer : Revista sciintelor medicale, 1909, Nos. 5 and 6. Zadro: Wiener klin. Wocli., 1909, No. 13. Berutti: Med. Klinik, 1909, No. 14. Avarffi: Gynakol. Rundschau, 1909, No. 9. Kroenig, Gauss, van Hoosen, Frogyesi, and Zweifel: Munch, med. Woch., 1909, No. 41. Stuelp: Klin. MonatsM. f. Augenheilk., 1909, No. 6. Beer: Dissertation, Freiburg i. Br., 1910. Beer enumerates the advantages and disadvantages of scopolamin- morphin anesthesia. This dissertation should be consulted by all inter- ested in scopolamin anesthesia. A LIST OF ANESTHETICS 815 Einne: Deut. med. Woch., 1910, No. 3, 110. Sick: Ibid., 1910, No. 9, 406. Hatcher's report to the Council of Pharmacy and Chemistry of the American Medical Association (J. Am. Med. Assn., Feb. 5-12, 1910) is probably one of the most conservative papers written on this subject. We quote from this paper: "Scopolamin and hyoscin are now considered interchangeable words. Scopolamin acts similarly to atropin in large doses, but in small doses has a different action. After small doses th'ere is a rise of blood-pressure but little change in the pulse rate. Clinically, it produces sleep without analgesia, if used alone. It is excreted by the kidneys. When used in combination with morphin, there is no antagonism in regard to its action on the respiration. "Statistics give us over thirty lives lost in an unknown number of administrations. These deaths have not occurred so frequently of late because very few attempt to use this combination without any other anesthetic. All insist that exceptional cases only can be narcotized with- out any chloroform or ether. When this occurs we are on dangerous ground. Schneiderlin, one of the earliest advocates of scopolamin and morphin in narcosis, recommends as high as 1/25 grain of scopola- min and IYq grains of niorphm in a space of li/4 hours. "Scopolamin and morphin may cause death from paralysis of respira- tion. When this occurs, artificial respiration is usually ineffective and sometimes useless.'" Hatcher states that no deaths had been recorded up to 1910 in which the dose did not exceed 1/130 grain of scopolamin and 1/6 grain of morphin. Ely (N. Y. Med. J., 1906, 799) reports the death of a patient from 1/100 grain of scopolamin and % grain of morphin. Contraindications to this form of medication are when from disease or accident the respiratory function is decreased, also in all cardiac dis- eases and other conditions which interfere with the circulation. Graves' disease also contraindicates its use. In acute or subacute nephritis a very rapid heart also indicates a smaller dose of hyoscin. Grave symp- toms sometimes arising after the operation is completed are probably some of the causes that led to the discontinuance of this form of anes- thesia. H. C. Wood, Jr., places the death rate at one in two hundred and fifty; Eoth places it at one in two hundred and twenty-two; an- other writer, at one in eighty. "Some of the minor after-effects, when used in large doses, are in- tense thirst, dryness of the mouth and throat, and difficulty in swallow- ing. In obstetrical cases 1/200 grain of scopolamin and 1/6 grain of morphin is the proper medication for the average case. The princi- pal advantage in obstetrical cases is that the memory is abolished, the patient being often surprised when told that it is all over. There is 816 ANESTHESIA often entire absence of pain, or this factor is greatly lessened. The prin- cipal objection to its nse is on account of the danger to the child. Some are born asphyxiated, or die asphyxiated a short while afterwards." The conclusions of Hatcher are as follows: (1) An attempt to use scopolarain and morphin alone without the addition of -some other drug is most dangerous. (2) There is no possible excuse for the employment of ready-made mixtures of scopolamin and morphin. They should be prescribed sep- arately as indicated by the patient's condition. Otto: Med. Klinik, 1910, No. 10, 380. Thomson: Ednl. Med. J., Dec, 1909; Beut. Med.-Ztg., 1910, No. 16, 276. Kiimmel: Klin. Monatsh. f. AugenheilJc, 1910, No. 4; Fortschr. d. Med., 1910, No. 9. Collins: J. Obstet. and Gynacol., 1910, No. 6, 549; J. Am. Med. Assn., 1910, 1051. Kuckert: Z. f. GehurtsUlfe u. Gyndlol., 1910, 66, No. 2. Faust: Deut. med. WocJi., 1910, No. 11, 508. See the papers by Sick, Otto, Euckert, Collins, Thomson, and Kiim- mel for the value of scopolamin-morphin in inhalation anesthesia. Kretz: Med. Klinilc, 1910, No. 40, 1568. Bosse and Eliasberg: Sammlung hlin. Vortrdge, 1910, Nos. 599 to 601; Gyndkologie, Nos. 215 to 217. Cremer: Med. Klinih, 1910, No. 28, 1092. Salzberger: Dissertation, Freiburg i. Br., 1910. Biirgi : Korrespond. f. ScUweizer Aerzte, 1909. Hauckold : Z. f. exper. Path. u. Therapie, 1910, No. 7, 743. Briistlein : Schweiz. Korresp.-Bl., 1910, No. 26. Ewald: Wiener med. Woch., 1910, 1214. Luxardo: Gazzetta degli ospedali e della cliniclie, June 9, 1910. Neu: MilncJi. med. Woch., 1910, No. 36, 1873. Neu made experiments to learn whether nitrous oxid anesthesia might not be improved by the previous use of scopolamin-morphin; the results obtained by experiments on animals showed that this was in fact the case. Korff : Med. Klinik, 1911, No. 2. Hastrup: Ugeskrift for Lceger, 1911, Nos. 1 and 2. Eood: Brit Med. J., 1911, 2, 652. Grigorjan: Wratschehuaja Gaceta, 1911, No. 31. BTiistlem: Zentr. Chir., 1911, 345. Eckert: Ibid., 1911, 857. Brant: Russkiy Wratsch, 1911, No. 13. Neuber: Z. f. drztl. Fortbildung, 1911, No. 12. Hippel: FortschriLte der Med., 1911, 229. A LIST OF ANESTHETICS 817 Bosse : Berl. Klinik, 1911, No. 272 ; Monats. f. Gehurtsh. u. Gyndlc, 1911, No. 3. Dietschky. Korrespond. f. Schiv. Aerzte, 1908, No. 15. Klauber: Milncli. med. Woch., 1911, No. 41, 2160. Gauss: lUd., 1911, 2355. Burkhardt: MAincli. med. Woch., 1911, No. 15, 778. Hagemann: Ihid., 1911, No. 28, 1427. Bjorkenheim : Zentr. Gyndlc. , 1911, No. 20, 759. On the value of scopolamin-morphin in midwifery, see: Freeland-Solomons : Brit. Med. J., 1911, i, 187. Strassmann: Berl. Jclin. Woch., 1911, No. 23. Iljin: BussTciy Wratsch, 1911, No. 12. Tichauer: Dissertation, Freiburg i. Br., 1911. Corbett: Brit. Med. J., 1911, 1, 868. On pantopon-scopolamin anesthesia, see: ■ Hani: Therap. der Gegenwart,, 1911, No. 2. Desehwanden: Korrespond. f. Schw. Aerzte, 1911, No. 4. Brunn: Zentr. Chir., 1911, No. 3. Briistlein: 7HJ., 1911, No. 10. Johannsen: Zentr. Gyndh., 1911, No. 19. Zeller: Miinch. med. Woch., 1911, No. 25. Eekert: Zentr. Chir., 1911, No. 25. Fowelin: 7&t^., 1911, No. 27. Simon: Miinch. med. Woch., 1911, No. 32. Kolde: 7&tU, 1911, No. 28. Aulhorn: ZHd, 1911, No. 12. Haeberlin: 7&iU, 1911, No. 33. Heinsius: Berl. Jclin. Woch., 1911, No. 41. Gray: Lancet, Sept. 2, 1911. Scopomorphin. — Sterilized euscopol- (q. v.) morphin solutions are marketed in glass tubes of 1 and 2 c. c. capacity. Each c. c. contains 0.0006 gm. euscopol and 0.015 gm. morphin hydrochlorid. The combina- tion is used for the production of total and semi-narcosis, and as an an- algesic and sedative. See Neuber: Z. f. drztl. Forth., 1911, No. 12, .340; Fonyo: Ohste. Aerzte.-Ztg., 1910, No. 2; Korff: Med. Klinih, 1911, No. 2; Salzberger: Zentr. f. ges. Therap., 1910, No. 10, 558; and Meyer: Miinch. med. Woch., 1910, No. 45, 2370. ' Septicylat. — This contains eugenol, methyl salicylate, geranoil, f or- ; maldehyd, and alcohol ; it is used in dentistry. Sicherheitsbenzin. — A mixture of 1 volume of benzin and 2 volumes of Carbon Tetrachlorid (q. v.). Sinecain. — Sinecain is a 3 per cent water solution of quinin hydro- chlorid, containing, in addition, 3 per cent of antipyrin and 0.05 mg. of adrenalin, intended for employment as a local anesthetic. 818 ANESTHESIA See E. Schepelmann : Med. Klinik, 1913, ISTo. 43. Skopomorphin. — See Scopomorphin. Scemnoforme. — See Somnoform. Soloid "Hemisine" Comp. c. Eucaino. — G.OOl gm. hemisin, 0.8 gm. sodium chlorid, and 0.2 gm. Eucain Ilydrochlorid (q. v.). Soluble Hypodermic Tablets Novocain, 1/3 grain. — Each tablet con- tains Novocain (q. v.), 0.02 gm. (1/3 grain). Soluble Tablets Novocain, 1 1/7 grains. — Each tablet contains novo- cain, 0.074 gm. (1 1/7 grains). Solution Atoxyl, 10 per cent, with Novocain, 1 per cent (sterilized). — Each 100 c. c. contaiji: atoxyl, 10 gm. ; and novocain, 1 gm. (each fluid ounce contains atoxyl, 48 grains; and novocain, 4:^^ grains), dissolved in distilled water. Somnoform. — This anesthetic, a mixture of ethyl chlorid, 83 parts; methyl chlorid, 16 parts; and ethyl bromid, 1 part (60 of ethyl chlorid and 5 of ethyl bromid, according to Gehes Codex, 1911, 328), is made in Bordeaux, France. In 1901 Eolland, of Bordeaux, read a paper on a new anesthetic he had discovered and named by him scemnoforme; this was a mixture of ethyl chlorid, 60 parts; methyl chlorid, 35 parts; and ethyl bromid, 5 parts (see Chem. Centr., 1903, i, 188). It was marketed by a London and by a Philadelphia firm. The latter firm later came under the control of a JSTew York company, but retained, as far as somnoform was concerned, the old name. Still later, after the decomposition of somnoform had been shown to be due largely to the ethyl bromid contained therein, this compound was omitted by the Lon- don firm from the mixture without notification being given to the Ameri- can company, and without change of label. The United States Govern- ment detected the inconsistency between the label and the product. Then the American firm asserted it knew nothing of it. When summoned by the Government, the firm had the product analyzed, found no ethyl bromid, pleaded guilty, and had a fine of $25.00 imposed (see Judgment No. 571, Food and Drugs Act). Then the present formula for somno- form was determined upon. It may be said, therefore, that somnoform, or scemnoforme, was formerly the same as the present Narcoform (q. v.), but at present is a mixture of ethyl chlorid, 83 parts; methyl chlorid, 16 parts; and ethyl bromid, 1 part. Somnoform was recommended by Eolland and Eobinson (Brit. Med. J., 1903, No. 2215, 1408) as an excellent and harmless anesthetic and narcotic, since it acted promptly, and, if allowed to act for 50 seconds to 2 minutes, did not give rise to undesirable sequelae, such as nausea and vomiting. Somnoform has been employed in a very large number of cases, especially in dentistry, as a substitute for nitrous oxid, as re- corded by Gross: Lancet, 1903, No. 4156, 1169; Secretan: Ibid., 1903, No. 4172, 1169; Cole: Presse med., 1903, No. 63, 572; Maguire: Lancet, A LIST OF ANESTHETICS 819 1903, No. 4174, 633 ; Lankester : Revue de Tlierap., 1903, No. 8, 272 ; Kirkpatrick: Med. Press and Circular, April 22, 1903; Gilmour: The Dental Rec, 1903, 496; Eonnet: Brit Dental J., 1903, 215; Galium: lUd., 1903, 267; and Vierthaler: Z. f. Stomatologie, 1903, No. 11, 349. All these writers concur in formulating the opinion that it induces com- plete relaxation of the muscles without cyanosis, and they state that the patients nearly always return to consciousness with a smiling coun- tenance; but, to quote Merck: Ann. Rep., 11, 168) : "It is, however, in its application in small operations that its utility will probably be great- est.'^ Eolland devised a special mask for the administration of somno- form. On the physiological action of somnoform, see Cole: Brit. Med. J., June 20, 1903, 1421; and Webster: Bio-Chemical J., 1906, 1, 328. Stenocarpin. — An alkaloid from the leaves of the "tear blanket" tree of Louisiana; said by Claiborne (*S'ct. Am. Suppl., No. 608) to possess local anesthetic properties. On the application of stenocarpin as a local anesthetic, consult the following literature : Claiborne: "A New Local Anesthetic," N. Y. Med. Rec, July 30 and Oct. 1, 1887. Goodmann : "Stenocarpin," Med. Rec, July 30, 1887. Jackson: "Observations on the Action of Stenocarpin, the New Local Anesthetic and Mydriatic," Am. Med. News, 1887, 255. Knapp : "Experiments with Stenocarpin," Med. Rec, 1887, 180. Morse: "Gleditschine (Stenocarpin)," Phila. Med. Surg. Rept., 1887, 701. Novy: "What Is Stenocarpin?" Am. pharm. Rund., 1887, 248. Stephen's Mixture. — An anesthetic mixture containing chloroform and alcohol, da; and Cologne Water, q. s. (Miiller: "Narkologie," 1, 493). Stovain or Stovaine (Benzoyl-Ethyl-Dimethylaminopropanol Hydro- chlorid. — Stovain is 2-benzoxy-2-methyl-l-dimethyl-amino butane hy- drochlorid, CH3.CH2C(CeH5C00) (CH3)CH.N(CH3)2.HC1 = C^.H^,- OgNCl. It is closely related to Alypin (which see) ; it was produced synthetically by Fourneau (hence its name) in 1904, and was first used in subarachnoid analgesia by Chaput. Stovain is prepared by causing a reaction of benzoyl chlorid on the a-dimethyl-amino-pentonal-5, which is itself the product of reaction of ethylmagnesium chlorid on methylaminoacetone. It crystallizes in small, brilliant scales, which melt at +175° C. (347° F.). It is ex- tremely soluble in water and easily in methyl alcohol and acetic ether, but requires 5 parts of absolute ethyl alcohol for solution and is only slightly soluble in acetone. It is quite stable and its solutions may be sterilized at -|- 115° C. (239° F.) without suffering decomposition. The 820 ANESTHESIA water solution is slightly acid to litmus, but is neutral to methyl orange. It is precipitated by all the alkaloidal reagents and is decomposed by even very dilute alkalies. It is incompatible with alkalies and all alkaloidal reagents. Actions Mild Uses. — Stovain acts as a local anesthetic. It has about the same power as cocain, but dilates the blood vessels, whereas cocain contracts them. It is only one-third to one-half as toxic as cocain. Stovain is also said to exert a tonic action on the heart. It is used as a local anesthetic; while most reports are favorable, one case of gangrene has been reported following the use of a 10 per cent solution. On the physiological properties of the methyl-, amyl-, phenyl-, and benzyl-homologues of stovain, see Veley and Synies : Chem. News, 103, 92, Fourneau has more recently prepared a new compound, the propyl ester of dimethyl-amino-oxy-benzoyl-isobutyric acid, which pos- sesses pronounced local anesthetic properties; it abolishes the contrac- tility of muscle less rapidly than does stovain or methyl-stovain, and has also less effect on blood pressure and on respiration. Dosage. — Internally, 0.002 gm. (1/30 grain), pill form. Locally it may be used in the eye in 4 per cent solution and applied to other mu- cous membranes, as in laryngology, in from 5 to 10 per cent solution. For hypodermic injections for local anesthesia, it can be used in 0.75 to 1 per cent solution. For further information on stovain, consult the following contribu- tions : Adam, C. : Milnch. med. Woch., 1906, No. 8. Alessandri: "Eachistovainisation," Congres de Chir. de Paris, Oct., 1906. D' Almeida: "La Stova'ine comme anesthesique," Acad. Nacional de Med., Eio de Janeiro, May 11, 1905. Andhelovici- Joanitescu : "Das Stovaine als intrarachidianes Anal- gesikum in der Yenerologie," Romania med., No. 22, 1905 ; abstracted in Milnch. med. Wocli., 1906, I^o. 13. Arnezzi: Brit. Med. J., 1905, No. 2320, 92. Audbert, A. : "La rachistovainisation en obstetrique," These de Paris, Apr. 4, 1906. i Babcock, W. W. : "Spinal Anesthesia with Special Eeference to the Use of Stovaine," Therap. Gaz., 30, 239, Apr. 15, 1906. "Spinal Anes- thesia; a Clinical Study of 658 Administrations," paper read before the Section on Surgery — Medical Society of the State of Penn., Cambridge Springs, Sept. 14-17, 1908. (Printed in Penn. Med. J., Aug., 1909.) The Obstetrical Society of Philadelphia — Meeting Thursday, March 4, 1909. Barton Cooke Hirst : "A Note on Sacral Anesthesia" ; "A Study of a Case of Spondylolisthesis." W. Wayne Babcock : Discussion. Badini: L'Ospedale maggiore, 1907, 261. A LIST OF ANESTHETICS 821 Bardescu: "La stova'me en chirurgie," Spitalul/ 1904:, Ko. 23. Barker, A, E. : "A Case ef Embolus Blocking the Bifurcation of the Aorta, Gangrene of One Leg. Amputation under Lumbar Analgesia/' London Clin. J., 28, No. 4 (May 9, 1906). Barker, A. E. : "A Report on Clinical Experiences with Spinal An- algesia in 100 Cases," Brit. Med. J., March 23, 1907. Baylac, M. J. : "Note sur la toxicite comparee de la stovaine et de la cocaine," Soc. de Biol., Paris, Feb. 3, 1906 (Revue Internat. de Med., 1906, No. 4). Becker: "Operationen mit, Riickenmarksanasthesie," Miincli. med. WocJi., 1906, No. 28, 1344. Bell, E. E. : "Stovaine, a New Local Anesthetic," N. Y. Amer. Vet. Rev., Jan., 1905, 28, No. 10. Benitez Fco, Cabrera : "La Stovaina," Rev. de la Escuela de Med. de la Hahana, 1906, 5, No. 3. Beurmann (de) and Tanon: "Emploi de la stovaine en dermatol- ogie," Bull. Soc. Frang. de Dermatol., 1904, No. 9. Bier: "Ueber den jetzigen Stand der Eiickenmarksanaesthesie, ihre Berechtigung, ihre Vorteile und Nachteile gegeniiber anderer Anaes- thesierungs Methoden," 34 Kongress der deutschen Gesellsch. fiir Chir- urgie, sApr., 1905. (Eef. Miinchen. med. Wchnschr., 1905, No. 23, 1117.) Billon, F. : "Sur un medicament nouveau, le chlorhydrate d'amy- leine," Acad, de Med. de Paris, March 29, 1904. Blondeau: "Sur I'emploi de la stovaine adrenalisee," J. de Med. d. Chir. pract., 76, No. 16, Aug. 25, 1905 ; Therap. Neuheiten, 1906, No. 1. Boeckel : Deut. m,ed. Woch., 1906, 1724. Bonachi : "Vingt.-trois cas de rachistovainisation," Bull, et Mem. d. la Soc. de'Chirurg. d. Bucharest, 8, 68. Bradburne: "Affections of the Eye (Stovaine)," London, Treatment, March, 1906. Braun: "Ueber Medullaranaesthesie," Munch, med. Woch., 1905, 1335; "Ueber einige neue ortliche Anasthetica," ibid., 1667; "Die Leistungen und Grenzen der lokal Anasthesie," Deut. med. Wocli., 1906, 42, 1668. Bruni, C. : "II metodo Cathelin nella cura dell incontinenza essen- ziale dorina," Ac. d. med. chir., Naples, 1905. Bruno, D. : "La Stovaina in Terapia oculare," Rev. internaz. de Clinica e Terapia, Naples, 1, No. 4. Busse : "Ueber die Verbindung von Morphium-Skopolamin Injek- tionen mit Eiickenmarksanasthesie bei gynakologischen Operationen," MUnch. med. Woch., 1906, 1858. Cavazzani and Balao Venturo: "Su alcune nueve maniere di anes- tesia generale e locale," Rev. veneta di sc. med., 1905, 25, No. 1. "Con- 822 ANESTHESIA tribute alia anestesia lombare e generale con la Stovaina e la Scopola- mina," ibid., 1906, S3, No. 7. Cernezzi: "L' Anestesia locale con la stovaina e con la miscela sto- vaino-adrenalinica nella chirurgia generale/' Riforma medica. Mar. 11, 1905. Chaput: "La stovaine, anesthesique local. Valeur de la stovai'ne comparee a la cocaine," Bull. Soc. hiol.. May 12, 1904. "L' Anesthesia rachidienne a la stovaine," Archives de Tlierap., Nov. 15, 1904. "Anes- thesie lombaire a la stovaine," ihid., April 1, 1905. "D'anesthesie totale au moyen de la rachi-stovainisation," Bull. Soc. hiol., July 6, 1907; Presse med., 1907, 131. "De la rachistovainisation," Soc. de chir., seance du 4 mars 1908 ; cf . Bull. Soc. chir., 1904, No. 30. Chartier : "La rachistovainisation en obstetrique," La Gynecol., Oct. 3, 1904. Chevalier and Scrini: "Sur Faction pharmacodynamique et clinique de la novocaine," Paris, Soc. d. Therap., July 27, 1906. Chiene, George : "The Use of Stovaine as a Spinal and Local Anes- thetic," Scot. Med. Surg. J., 1906, No. 3. Christie, W. W. : "The IJse of Stovaine as a Local Anesthetic in Throat and Nose Operations," Glasgow Med. J., Feb., 1906. Cisler, Jos. : "Nova anaesthetika vrhino laryngologie," Csasopsis lekaruv cesJcy, Prague, Jan. 3, 1906. Coakley, C. G. : "Eeport on the Use of Stovaine," N. Y. Acad. Med., Feb. 22, 1905 ; Zahntechn. Reform., 1906, No. 3. Coderque : Rev. de med. y dr., Sept. 7, 1907. Cohn: "Medullaranasthesie in der Geburtshilfe," Mediz. Gesell. in Giessen, Jan. 30, 1906 ; Deut. med. Woch., 1906, 22. Couteaud: Bull. d. I'Acad. d. Med., 1908, No. 26. Czermak : "Nouvelles observations demontrant I'inocuite de la rachi- stovainisation pour les reins," Zentralbl. f. Chir., Feb. 15, 1908. Czerny : 3J/. Kongress der Deut. Gesellsch. f. Chir., Apr., 1905. Dean, H. P. : "The Importance of Anesthesia by Lumbar Injec- tions in Operations for Acute Abdominal Disease," Brit. Med. J., 1906, No. 2367. Demaillasson : "Les injections analgesiantes 'loco dolenti' dans les nevralgies peripheriques," These de Paris, 1905. Deetz: "Erfahrungen ueber 360 Elickenmarksanasthesien mit Dem- onstrationen," Munch, med. Woch., 1906, No. 28; Z. f. Kranhenpf., 1906, No. 3. . Delattre, G. : "Accidents consecutif s a I'introduction des substances medicamenteuses dans le liquide cephalorachidien," These de Paris, 1905. Deupes, E. : "La stovaine : etude expef imentale et clinique," These de Toulouse, 1906. A LIST OF ANESTHETICS 823 Dion, Gr. : "Stovaine; son cmploi en chimrgie oculaire/' jf7ie.se de Bordeaux, 1905. Doleris : "La stovaine," Soc. d'Ohstetriq., de Gynec. et de Fediair., Paris, July 11, 1904. Doleris and Chartier : "La raehistovainisation en gynecologic," La Gynecol., Feb., 1905. Donitz: "Technik, Wirkung u. specielle Indication der Eiicken- marksantisthesie," Arch. f. Jdinisch. Chir., 1906, 77, No. 4. Donitz: "Wie vermeidet man Misserfolge bie der Lumbalaniisthe- sie," Munch, med. Woch., 1906, 1339. Dubar : "La stovaine en oto-rhino-laryngologie," Progres med., Nov. 26, 1904; Rev. de Therap., 1905, 57, No. 2. DufPour : "Etude sur la sterilisation et I'emploi des solutions hypo- dermiques," Toulouse, July, 1905, These. Elting, A. W. : "The Method and Indications for the Use of Spinal Anaesthesia," Albany Med. Ann., May, 1906. Eeliziani: "Sull'anestesia rachistovainica," Policlinico, 1908, sez. j)rat., fasc. 7. Fernandez, J. S. : "Le estovaina en nuestra oftamologica," Cro- nica med.-quir. de la Hahana, May, 1905. Finckelnburg : "Neurologische Beobachtungen und Untersuchungen bei der Eiickenmarksanasthesie mittelst Kokain und Stovain," Miinch. med.Woch., 1906, No. 9, 397. Fischer, E. : "Ueber Stovaine in der oto-rhino-laryngologischen Praxis," Deut. med. Ztg., 1906, No. 38. Foisy: "La stovaine, ses advantages, ses inconvenients, son incom- patibilite avec I'adrenaline," Tribune med., 1904, No. 37. Forns: "La estovaina in obstetrica," Rev. d. I. especialidades med., Madrid, Sept. 20, 1904. Fourneau, E. : "Sur les amino-alcools tertiares," Acad. d. Sci., Paris, Feb., 1904; "Anesthesiques locaux," Rev. gen. d. Sci., Sept. 30, 1904; Bull. Sci. Pharmacol., 1904, No. 9. Fourneau, C. : "Un nouvel anesthesique local. La stovaine," J. Pharm. Chim., Aug. 1, 1904. Freund: "Weitere Erfahrungen mit der Eiickenmarksnarkose," Miinch. med. Woch., 1906, 1109. Fromaget and Dion: "Action mydriatique de la stovaine," Presse med., Oct. 1, 1904. Galceran, A. B. : "La estovaina como anestesico y analgesico," Bar- celona, Archives d. Therap., 1905, No. 11. Galletta: "Contribuzione clinica alia rachistovainizzazione," Poli- clinico, 1908, sez chir., fasc. 1 and 2. Garcia Tapia : "La stovaine ; Sus applicaciones in oto-rinilarin- gologia," Bolet. di laringol., Madrid, Nov. 3, 1904. 824 ANESTHESIA Gaudier : "De la rachi-stovainisation chez les enf ants," Soc. de Chir., seance du 16 Janvier, 1907. Gaviss: "Die JSTarkose in der operativen Geburtshiilfe," Tlierap. der Gegenwart, 1906, 453. Gemnseus: "Das Stovain,'' Dissert., Bern, 1905. Gironi : "Contribution clinique a la rachistovainisation," Gaz. degli ospedali, July 7, 1907. Goldscheider : Tlierap. der Gegejiwart, 1905, No. 12. Greiffenhagen : ZentralU. f. Cliir., 1906, No. 19. Hackenbruch : "Lumbalanasthesie," Wiesbaden Centralbl. f, CJiir., 1906, No. 14. Halbron and Chartier: "Note sur la reaction meningee apres la rachistovainisation," Paris, Feb., 1905. Heinecke and Lowen : "Lumbalanasthesie niit Stovaine und Novo- cain," Brunssclie Beit. z. Id. Chir., Leipzig, 1906, 50, Part 2. Hermes: "Eiikenmarksanasthesie," 34th Deut. Chir. Kongress in Berl., Apr., 1905 ; "Weitere Erfahrungen iiber Eiickenmarks-anasthesie mit Stovaine und Novocain," Med. Klinilc, 1906, No. 13. Hildebrandt: "Die Lumbalanasthesie," Berl. Tclin. Woch., Aug. 31, 1905. Holzbach: "80 Lumbalranasthesien ohne Versager," Milncli. med. Woch., Jan. 22, 1908. Hosemann: "L'Inocuite pour le rein de la rachi-stovainisation," ZentralU. f. CUrurg., Jan. 10, 1908. Huchard: "Quelques Faits therapeutiques sur la stovaine," Acad, de Med., Paris, July 12, 1904; J. des Practiciens, 1904, 33. Impallomeni, G. : "Le iniezoni intramuscolare di salicilato sodico e stovaina. Loro applicazioni therapeutiche," II Policlinico, May 6, 1906, 13, No. 18. Jonnesco : "Sur la rachistovainisation," Bull, et Mem. de la Soc. de Chir. de Bucharest, 8, 60-63; "Eemarks on General Spinal Analgesia" (letter to the editor), N. Y. Med. J., Jan. 1, 1910; "Eemarks on Gen- eral Spinal Analgesia," Brit. Med. J., Nov. 13, 1909 (Abstr. N. Y. Med. J., Dec. 4, 1909, 1133) ; "General Eachiansesthesia," Med. Times (N. Y.), Feb., 1910; "Concerning General Eachianaesthesia," Am. J. Surg., Feb., 1910. Joris, L. : "La stovaine," Bollet. dell. Assoc, medica. Tridentina, Jan. 1, 1906. Kamenzave, L. : "La Stovaine, etude experimentale," These de Geneve, 1905. Kendirdjy, L. : "L'Anesthesie chirurgicale par la stovaine," Paris ; Masson et C, edit. 1906. "General Indications for and Technique of Lo- cal Ansesthesia," J. d. Med. et d. Chir. Pratiques, Apr. 10, 1909, 80, No. 7. A LIST OF ANESTHETICS 825 Kendirdjy and Bertreaux, E. : "L'Anesthesie chirurgicale par in- jection sousarachinoidienne de stovaine," Fresse med., 1904, 6G0. Kendirdjy and Burgaud, V. : "Cent quarante nouveaux eas de rachistovainisation," ibid., M^sij 31, 1905; Allg. m,ed. Zentral.-Zig., 1905, No. 24. Koenig, C. J.: "L' Analgesic locale par le stovaine," Arch. Intern, de Laryngol., 1905, 18, 5, 9. Krecke: Munch, med. Woch., 1906, No. 6. Kroemer: "Beckenerweiternde Operationen," Mediz. Gesell. in Giessen, Jan. 30, 1906; Deut. med. Woch., 1906, 900. Kroner : "Ueber einige neuere Arbeiten zur Lumbalpunktion iind Lumbalanasthesie/' Therap. der Gegenwart, 1906, 361. Kroenig, M. : "Denx cents cas de narcose mixte par combinaison de la scopalamine-morphine avec la rachistovainisation," Presse med., Apr. 14, 1906. Kroenig and Gauss: "Observations anatoiniques et physiologiques au cours d'un premier millier de rachi-anasthesies," Miinch. med. Woch.,. Oct. 1 and 7, 1907,. Kugel, L. : "Stovaine ein neues Anasthetikum," Wien. Jclin. therap. Woch., 1906, No. 7. Kiimmel: "Stovainlumbalanasthezien," Deut. med. Woch., 1906, 126. Lacceti, C. : "A proposito dell'anestesia locale stovainica in chirur- gia," Gaz. internaz. di m,edic., July, 1906. Laewen: Beitr. zur Min. Chir., 1906, 2, 50. Lang: Deut. med Foc/i., 1906, No. 35. Lasio: "La rachistovainisation en chirurgie urinaire," Clin. Chir., 1907, fasc. 9. Lapersonne, F. de: "Un nouvel anesthesique local, la stovaine," Presse med., 1904, No. 30, 233. Launoy, L. : "Action du chlorhydrate d'amyleine sur le mouvement ciliare/' Acad, des Sciences, Paris, July 11, 1904. Launoy and Billon: "Sur la toxicite du chlorhydrate d'amyleine," Acad, des Sciences, Paris, 15 May, 1904; Compt. rend., March 15 and July 11, 1904; Presse med., 1904, 368. Lazarus, .P. : "Zur Lumbalanasthesie," Berl. Min. Woch., Mar. 19, 1906. Lepnender : "Sur I'anesthesie locale et la sensibilite du corps et des tisms," -Oentralh. f. C/wV., .1906, No. 9. Loeser: Deut. med. Woch., 1906, 483. Loffler: "Lumbalanasthesie mit Stovaine," Franhfort-Mi'mch. med. Woch., 1906, 95. , LohmanUj W. : "Das Stovaine in der Infiltration- Anasthesie," Fortschr. k Mediz., Nov. 20, 1905, No. 33. 826 ANESTHESIA Lohrer: "Zur Behandlimg hysterischer Kontrakturen der unteren Extremitaten durch Lumbalanasthesie," Munch, med. Woch., 1906, 1568. Lucangelli, G. L. : "La Stovaine I'Alipina," Gaz. med., Dec, 1905. Luke, T. D. : "Stovaine : a Synthetic Analgesic," Scot. Med. Assn. J., Edinburgh,, 1905, 17, 143. McGavin : "A Eeport of 250 Cases of Spmal Analgesia by the Use of Stovaiue-Glucose Solution," The Practitioner, Aug., 1909. McKenzie, D. : "The Local Anaesthetic Action of Stovaine," Brit. Med. J., 1906, Ko. 2367. Marchetti, L. : "La stovaina como anestetico locale nella practica chirurgia," Gaz. degli osped. e. del. din., ISTov. 26, 1905. Martin, Collier F. : "The Use of Spinal Anesthesia in Rectal Sur- gery," The Proctologist, Sept., 1909. Mercier, 0. F. : "L'Anesthesie chirurgicale par la stovaine," Mon- treal, L'Union med. du Canada, May 1, 1906, 35, No. 5. Meyer, A. : "Zwei neue Lokalanasthetica in der rhinolaryngolo- gischen Praxis," Therap. Monats., 1905, No. 5, 240. Milko: "Spinalanalgesie mit Stovaine," Deut. med. Woch., 1906, 1400. Mosetig: "La stovaine," Deut. Naturforsch. Versammlung, 1905. Miiller, Benno : "Stovaine als Anasthetikum," Sammlung Jclin. Vor- trdge, 1906, 15, No. 428, No. 8, 495. Narewski : Zahndrztliche Rundschau, 1907, No. 19. Nogue, E. : "La stovaine en stomatologie," Arch, de Stomatolog., 1904, Nos. 4 and 5. Noland, Lloyd: "Stovaine Spinal Angesthesia, a Report of Twenty Cases," Ann. of Surg., Apr., 1910. Nigoul, M. : "Constatations cliniques au sujet de la stovaine," Con- cours medicale, Paris, June 24, 1905. Ostwald, T. : Berl. klin. Woch., 1906, No. 1. " Pauchet, Amiens: "La chirurgie rurales; rachistovainisation," La Clinique, 1906, 633. "Petite chirurgie; traitement du panaris," La Clinique, 1906, 681. Penkert: "Lumbalanasthesie im Morphium-Skopolamin Dammer- schlaf," MUnch. med. Woch., 1906, 646 ; 1907, No. 25. Perez : II Policlinico, 1907, No. 3. Piedallu, R. : "La stovaine," These de Paris, July, 1905. Piga, A. : "Contribucion al estudio de los efectos fisiologicos y tera- peuticos de la estovaina," Madrid, Los nuevos remedios, Apr. 30 and May 30, 1905. Pochhammer : "Zur Teknik und Indikationstellung der Spinal-anal- gesie," Deut. med. Woch., 1906, No. 24. Poenaru Caplescu : "Rachistovaiue," Spitalul, 1905, 19-20 j "La sto- vaine en chirurgie," ihid., 1904, 21-22. A LIST OF ANESTHETICS 827 Poenaru: Deut. med. Wocli., 1910, No. 8. Poinsot, A. : "La cocaine en art dentaire/' These de Paris, 1905. Pont, A,: "A propos d'un nouvel anesthesique local, la stovaine," Bull, de Lyon med.. May 15, 1904. Polini, Gr. : "La stovaina in chirurgia," Gazz. internaz. di medic, Naples, Oct., 1905. Poth, H. : "Ueber Stovaine als lokales Anaesthetikum in der kleinen Chirurgie," Med. Klinik, 1905, No. 15. Pouchet: "fitude pharmacodynamique de la stovaine," Acad, de Med., Paris, July 12, 1904; Eevue de Therap., 1904, 543. Pouliquen : "La rachistovainisation," These de Paris, 1905. Preindlsberger : Allg. med. Zentral-Ztg., 1905, No. 42, 808. Preliminary Report of the Anesthesia Commission of the American Medical Association. Transactions of the Section on Surgery and Anat- omy of the American Medical Association, 1908, 426-427, A. M. A. Press. Pringle : "Notes of an Experience of Stovaine as a Spinal Analgesic in 100 Cases," Brit. Med. J., 1907, No. 2427, 12. Pussep : Arch. f. Psych., 1911, No. 48, 2. Eabourdin, A. : "Topographic des alterations sensitives dans rachi- stovainisation," These de Paris, 1906. Eahn, A. : "Die Ersatzmittel des Kokains," Pharm. Cent., Sept. 28, 1905; "Ueber Stovaine in der Lumbal-Ansesthesie," Deut. Aerzte-Ztg., Apr. 15, 1906. Eavant: "Anesthesie chirurgicale limitee a la region genito-pe- rineoanale par I'injection intra-rachidienne de solution concentree," Soc. de Biol., seance du 22 juin, 1907. Eeclus, P.: "L'Analgesie locale par la Stovaine," Academic de Mede- cine, Paris, July 5, 1904; Revue de Therap., 1904, 595. "La Stovaine," Presse med., Jan. 3, 1906. Eoith: Munch, med. Woch., 1907, No. 19. Eoyet : "Behandlung der Ozsena mit Stovaine," Wiener hlin. therap. Woch., 1906, No. 10. Euschhaupt: "Lumbalanasthesie mit Stovaine," Med.- Gesell. in Giessen, Feb. 20, 1906. Euthon : "Sur un nouvel anesthesique : la stovaine," These de Paris, 1904. Sandberg, J. : "Spinalanalgesie," Med. Rev., Dec, 1905. Saratucci: II Policlinico, 1907, No. 9. Sauvez, E. : "Un nouvel anesthesique local : la stovaine," Soc. d'Odontologie, Apr. 9, 1904; Rev. internat. Med. et Chir., 1904, 191. "L' Anesthesie locale pour I'extraction des dents," Archiv. de Therap., Aug. 1, 1905. "Quelle est la meilleure methode d'anesthesie locale pour I'extraction des dents ?" La clinique, Aug. 3, 1906, 505. 828 ANESTHESIA Schiff: "Ueber Stovaine als lokales Ansesthetikum/' Deut. med. Woch., Aug. 31, 1905. Schwarz : Zentr. f. Cliir., 1907, No. 13. Scrini : "Precis de therapeutique oculaire," Paris : G. Steinheil, edit. 1904. "La stovaine," Arcli. d'OphlJialmol., June 15, 1905. "Sur la sto- vaine," Paris, Soc. de Therap., Oct. 10, 1906. Silbermark, M. : "Ueber Spinalanalgesie," Wiener Tclin. Woch., Nov., 1904,- No. 46. Sinclair, A. : "Gangrene of the Skin Following the Use of Stovaine, a New Local Anesthetic," Cutan. Dis. inch Syph., 1904:, 13, 307, 310; Tlierap. Monats., 1905, No. 11, 595. .' ■• Sluss, J. W. : "Spinal Analgesia," Indiana Med. J., June 12, 1906. Sonnenburg: "Eiickenmarksanasthesie naittels Stovaine," Deut. med. Woch., 1905, No. 9. j; ' Spiller and Leopold: Deut. med. Woch., 1910, 1292. Stephenson: "Stovaine: a New Local Anesthetic," Ophtlialmoscope, Nov., 1904; Bev. de Therap., 1905, 128. Tilmann, 0. : "Lumbalanasthesie mit Stovaine," Berl. Tclin. WocTi., Aug. 21, 1905. v. ' Tomai, G. : "L'anestesia stovainica," Giorn. internaz. d. sc. mediche, Feb. 28, 1906. Trautenroth: Deut. med. Woclt., 1906, No. 7. Tuflier, Th. : "Die Riickenniarksanasthesie mit Stovaine," Klin, tlierap. Woch., 1905, 378. Varvaro, E. : // PolicUno, 1906, Nos. 6, 7, 8. Wainwright, J. M. : "On the Yalue of Spinal Analgesia in Shock,"' Pe/m. ilieii. J., Nov., 1905. Wendel: "Die modernen Bestrebungen zur Verminderung der Narkowengefahr," Munch, med. Wocli., 1906, 1601. Wilms: "Heilung hysterischer Kontrakturen durch Lumballah- mung," Deut. med. Woch., June 14, 1906. Wolff, L. : "Ein neues cocainfreies Injections-Anasthetikum,"; AZ/^. mediz. Central. -Ztg., 1906, No. 13. , }• Woskresenski, A. W. : "Ueber lokale Stovaine Anasthesie," Fxiftschr. der Med., 1905, 506. Zahradnicky: "The Eesults of Spinal Anesthesia, Especially in Laparotomy," Archiv f. hlin. Ohir., 98, No. 2; Extract in Therap. Oaz., Sept. 15, 1909. Zernik (F) : "Stovaine," Apoth.-Ztg., 1905, No. 19. Zwintz (J.) : "Ueber Stovaine, ein pharmako-dynamische Studie," Wien. med. Presse, Feb. 4, 1906, No. 5. Stovain Billon. — Contains, in 1 c. c, 0.00013 gm, epirenin borate, 0.04 gm. stovain, and 0.0011 gm. sodium chlorid. Stovain with Strychnin. — On the use of stovain with strychnin for A LIST OF ANESTHETICS 829 spinal anesthesia, see Z. fur Cliir., 107, 1-3 ; Therap. Gaz., June 15, 1911. Strophanthin. — Strophanthin (strophanthinuni, strophanti n) is, ac- cording to the United States Pharmacopoeia, a glucosid, or mixture of glucosids, obtained from strophanthus ; it was made official in the eighth revision of the Pliarmacopceia. It is officially described as a white or faintly yellowish crystalline powder, containing varying amounts of water of crystallization, which it does not lose entirely with- out decomposition. Its taste is intensely bitter, and it is permanent in the air. It is very soluble in water and in dilute alcohol, but is less soluble in absolute alcohol, and is nearly insoluble in ether, chloroform, and benzene. It commences to fuse at -\- 170° C, and is not completely melted until the temperature of -|- 190° C. is reached. Its solutions are dextrogyrate, and are neutral to litmus. Fraser {Am. J. Pliarm., 1889, 532) found that strophanthin was difficult to separate, but obtained it pure by a process depending upon the formation of a tannate and sub- sequent decomposition by lead oxid. It yielded, upon analysis, results corresponding to the formula CooHg^Oio- Thoms (Ber., 1898, 534) pre- pared pure strophanthin. Arnaud gave its formula as Q^-J1^^0-^^o, and his results were confirmed by Kohn and Kulisch; Feist reported C^oHgeOg. Thoms found that the strophanthins as obtained from different species differed somewhat in composition; he proposes designating them as fol- lows: k-stropliarithin when obtained from S. komhe; g -strophanthin when prepared from S. gratus; e-strophanthin when from S. emini; and h-strophanthin when from ^S*. hispidus. On the properties of strophanthin, see Hardy and Gallois : J. Pharm. Chim. (3), 25, 176, and Fraser: Pharm. J., July 23, 1886. On the physiological action of strophanthus preparations, see Steinach: Wiener klin. Woch., 1888. The local anesthetic action of strophanthin and Ouabain (q. v.) has been discussed by Panas: Bull, de I'Acad. de Med. de Paris, 1890, No. 7. Sturmann's Solution. — A local anesthetic containing : Cocain hydro- chlorid, 1.0; tincture iodin (decolorized), phenol, aa., 0.3; glycerin, 10.0; water to 100.0; and 2 drops of a 1 : 1,000 suprarenin hydrochlorid solution are added per c. c. Subcain. — A solution containing 1 per cent cocain, 0.0065 suprare- nin borate, 0.1 per cent salicylic acid, 0.8 per cent sodium chlorid, and eucalj'ptol. Subcutin (Subcutol; Ancesthesinum solubile; paraphenol sulphonate of- ansesthesin; paraphenol sulphonic acid of para-amidobenzoic acid ethyl ester). — A local anesthetic used like anoisthesin. „ , . / /NH2.S03H.C6H40H\ Subcutm.— I CeHZ 1 V ^COOCjHs / is a fine, white, needle-shaped 830 ANESTHESIA crystalline powder, melting at + 195.6° C, and soluble in cold water, 1:100, and in warm water (body temperature), 2.5:100. On contact with the tongue, it produces a sensation of numbness. It is stable in solution and on boiling — an advantage over cocain, which does not keep so well. On the chemistry of subcutin, see Eitsert : Pharm.-Ztg., 5Jf:, 797. The fact that Ancestliesin {q. v.) is almost insoluble in water and that it therefore is not well adapted for the preparation of media suitable for injection led Eitsert to study a whole group of anesthesin compounds with a view of determining whether any of them was endowed with greater solubility, and yet mild in its action and free from irritat- ing properties. He ascertained that the phenol sulphonate, or subcutin, answered these requirements. It has been shown that subcutin exerts an inhibitory action on the propagation of the pathogenic micro-organisms of typhoid and cholera. It is said to be free from all untoward by-effects; and it has been demon- strated experimentally that doses such as are not required in major operations are always well tolerated. It may be said, therefore, that subcutin is nontoxic for all practical purposes, especially since experi- ments on animals demonstrated that 1.6 gra. per kg. of body weight might be administered without danger. See Ancesthesin. On subcutin, see es- pecially Becker: Miinch. med. Woch., 1903, 50, No. 20, 857. "Sub- cutin-mundwasser" is a 2 per cent subcutin solution. Sulzberger's Local Angesthetic. — Nathan Sulzberger, in U. S. Patent 949,134, February 15, 1910, announces a local anesthetic, consisting of a 10 per cent solution of cocain in phenyl acetate with a very small per- centage of adrenalin. Ethyl acetate and phenyl stearate are also claimed as solvents of menthol or cocain. Summopon. — This preparation contains the alkaloids of opium (Chem.-Zentr., 1912, 1,1672). 8ee Pantopon. Suppositoires Adreno-styptiques. — Each contains 0.00035 gm. adre- nalin and 0.2 gm. ansesthesin-stovain. These are used in the treatment of hemorrhoids. Suprarenal-tonogen. — A water solution of 0.1 per cent suprarenal extract, 0.5 per cent chloretone, and 0.7 per cent sodium chlorid. Suprarenin. — o-Dioxyphenylethanolmethylamin [ (OH) 2CeH3.CH0H.CH2.NHCH3] is a grayish white powder which has a melting point of -\- 210-212° C. It is a hemostatic and astringent, and is used in combination with vari- ous local, anesthetics, as, for example. Novocain (q. v.). Synthetic su- prarenin has the same uses; suprarenin borate and hydrochlorid are also used in combination with cocain and other local anesthetics. Suprarenin-cocain Tablets. — See Braun's Suprarenin-tabletten. Terpentinchlorhydrate. — See Terpin Hydrochlorid. Terpentinkampfer. — See Terpin Hydrochlorid. A LIST OF ANESTHETICS 831 Terpin Hydrochlorid (Terpiiichlorliydrate). — CjoITio-HCl is a cam- phoraceous mass, melting at -\- ]25° C; it is said to bo used as a local anesthetic in combination with phenol. Tetrachlorethane (Sym.). — Symmetrical tetrachlorethane (acetylene tetrachlorid ; "westron'"), C2H2CI4, is slightly anesthetic (Clement and Reviere: "Caoutchouc ct Gutta-percha," 7, 4021) ; but under the con- ditions of its use as an extraction material and solvent in factories, its narcotic effects, as well as those of trichlorethylen, which is less active physiologically, are said to be less than those of some of the other solv- ents (see, on this point, Chem.-Ztg., 32, 529). Tetrahydronaphthalene. — According to Brissemoret (Compt. rend. Soc. hiol., 69, 497), this compound has a narcotizing power on such warm-blooded animals as the rabbit. Tetramethyldiaminodimethylethylcarbinol Cinnamate Hydrochlorid. — This is an alypin, in which cinnamic acid takes the place of benzoic acid; it is said to produce an anesthetic effect lasting twice as long as that effected by the same quantity of cocain (Farbenfabriken vorni. Friedr. Bayer & Co., German Patent 173,631). Thibault's Local Anaesthetic. — In 1907 Thibault suggested the em- ployment of quinin and urea hydrochlorid as a local anesthetic in opera- tions usually performed with cocain. See Quinin and Urea Ilydroclilorid. Thymocain. — This local anesthetic, said to be without toxic action when used subcutaneously, contains about 1 per cent cocain hydrochlorid and 1 per cent sodium chlorid in water solution, also very small amounts of alcohol, thymol, and a suprarenal gland preparation. Thymoform. — This preparation, intended for use in the treatment of teeth, contains thymol, alum, formaldehyd, and creosote. Tonocainum Suprarenale Richter. — A sterilized tonogen-eucain solu- tion. Tonogen Suprarenale Richter.' — A solution (1:1,000) of extract of suprarenal gland with an addition of 0.5 per cent of chloretone and 0.7 per cent sodium chlorid. Townley's Anodyne Mixture. — James Townley ("Parturition AYith- out Pain or Loss of Consciousness," London, 1863) recommended the employment of an anodyne mixture composed of "alcohol, two ounces; one drachm of aromatic tincture; with sufficient chloroform added short of the production of a turbid state of the fluid.'^ The formula of the aromatic tincture was as follows: "One drachm of nutmegs; two drachms of cloves; pterocarp chips, a drachm and a half; water, four ounces; alcohol, five ounces." This mixture was successfully used by Townley in obstetrical practice for the purpose of blunting the sensibil- ity to pain without the abolition of consciousness. Trichlorethane. — a-trichlorethane (monbchlorethylene chlorid). 832 ANESTHESIA CH0CI.CHCI2, is a colorless liquid, boiling at -|- 37° C. The readiness with which it is formed by the action of potassium hydroxid upon tri- chlorethane suggested the hypothesis that the anesthetic effects of this last are really attributable to the liberation of dichlorethylene in the blood. This view was advanced by Tauber, of Jena, who experimented with the isomeric trichlorethanes for the purpose of determining their anesthetic value. His observations were made upon frogs, pigeons, guinea-pigs, rabbits, and dogs; a few drops were sufficient to produce complete anesthesia in the smaller animals. ' ■■ Methylchloroform (mono-chlorethylidene chlorid), CH3.CCI3. — This was also studied by Tauber. Administered in the form of vapor to frogs and rabbits it produced a satisfactory anesthesia, without any marked effect upon respiration or circulation. Upon himself Tauber experimented by inhaling the vapor of about 20 gm. under the super- vision of von Langenbeck. There was no stage of excitement preceding anesthesia; respiration remained undisturbed; the pulse did not exceed eighty-four beats per minute; it was regular, and exhibited no evi- dence of diminishing blood pressure. Complete anesthesia was reached in five and a half minutes, and it continued for 10 miputes longer. Vomiting occurred soon after the recovery of consciousness, breakfast having been eaten about two hours before the experiment. A feeling of general discomfort persisted for about an hour, after which it disap- peared, leaving no unpleasant effects behind. See Brit. Med. J., Nov. 13, 1880. Trichlorethylene Dichlorid. — See /Ether arkestheticus aranii. Trichlorurum Formili, — See Chloroform. Trimethylbenzoxypiperidinum hydrochloricum. — See Eucain-B. Trimethylethylene. — Prepared, according to von Mering (Eng. Pat. 11,844, 1891), from tertiary amyl. alcohol by action of : water-abstract- ing agents; claimed by him to be superior to "amylene" from fusel oil. See Pental. ■ ' , ' .: ■ Tropacocain or Tropacocain Hydrochlorid ( Tropacocaihse Hydro- chloridum) . — Benzoylpseudotropein hydrochlorid, tropein, tropacocain hydrochlorid [C8Hi,N0(C,H50)HCl = Ci,Hi„N0'2.HCl] is the hydro- chlorid of synthetic tropacocain. It was found' in 1891 by Giesel (Pharm.-Ztg., 1891, 419) in the leaves of the Japanese coca plant, and subsequently it was examined by Liebermann very accurately (Ber., 1891, 2336; 1892, 927). Liebermann also succeeded in reproducing it by synthesis from its components, and in this manner he obtained a purer and more active preparation than the natural vegetable base. Willstatter (Ber., 29, 393, 936, 1575, 2216) indicated a method by which benzoylpseudotropeine might be obtained from tropin, and this method was patented and a cheaper preparation was obtained. Pseudotropin-Liebermann. — Pselidotropin-Liebermann is obtained A LIST OF ANESTHETICS 833 from tropinon or from tropin by electrolytic reduction, and from this the benzoyl derivative is obtained, and this is converted into tlie hydrochlorid. It forms colorless, needle-shaped crystals, melting at -f 271° C. (519.8° F.). It is readily soluble in water, and its solution keeps well for several months. Heated in the presence of hydrochloric acid, it is split up into benzoic acid and tropin. Its incompatibilities are the same as those of the alkaloids in general. Benzoylpseudotropein. — Benzoylpseudotropein was tested physiologi- cally by Chadbourne (Brit. Med. J., 1892, 402) soon after its discovery, and it was he who recommended it under the name of tropacocain as a local anesthetic and cocain substitute. He found it to be less than half as poisonous as cocain, and he regarded it in particular as a much milder poison in its action upon muscles and motor centers. Its solutions may be boiled indefinitely for purposes of sterilization. Tropacocain Hydrochlorid. — Tropacocain hydrochlorid is now em- ployed as a local anesthetic instead of cocain hydrochlorid; the solution is said to be more stable, easily sterilizable, and to have a less depressing action on the heart. It is used in ophthalmology, dentistry, general sur- gery by the Schleieh infiltration method, in regional anesthesia accord- ing to Oberst, and in lumbar anesthesia in accordance with Bier's method. Dosage. — It is applied in 3 to 10 per cent water solutions containing 0.6 per cent sodium chlorid. On Tropacocain Hydrochlorid, see the following contributions: Chadbourne: Therap. Monalsh., 1892, 471; Brit. Med. J., 1892, Ko. 2. Schweigger and Silex : Therap. Monatsli., 1892, 473. Pinet and Viau-. Comm. faites a la Soc. d'Ontolog. de Paris., Dec. 6, 1892; Jan. 10, 1893. Hagenschmidt : Sem. mid., 1893, No. 6. Ferdinands : Brit. Med. J., 1893, 1318. Groenouw: Deut. med. Woch., 1893, No. 26, 331. Bockenham: Sem mid., 1893, 536; Brit. Med. J., Nov. 18, 1893. Veasey: N. Y. Med. J., Nov. 25, 1893. Seifert: Internat. hlin. Rundschau, 1893, No. 8. In 1893 a 3 per cent solution was generally used to produce local anesthesia, and it was observed that stronger solutions, such as a 5 per cent one, under certain circumstances, caused undesirable results. Vamossy: Therap. Woch., 1896, No. 9. Hattyasy: Oest.-ungar. Vierteljalirs. f. Zahnhlhde, 1896, 161. Eogman: Cli^i. ophthal., 1897, Nos. 17 and 19. Blaskovics : Pest. med. chir. presse, 1896, No. 50. Dillenz: Dissertation, Ziirich, 1897. Custer: Miinch. med. Woch., 1898, No. 32. 834 ANESTHESIA Braun: Central}), f. Chir., 1897, 'No. 17; Yolkmann's :" Sammlung Jclin. Vortrilge, 1898, No. 228. Hilbert: Ophthalmiat. Klinik, 1899, No. 11. Schmitt : Bev. med. de VEst, 1898, No. 20. Brieglieb: Z. f. praktische Aerzte, 1899, No. 6. Dorn: ^ Odontol. Blatter, 1899. Seifert: Inter. Jclin. Rundschau, 1899, No. 8. Lang: Gyogydszat, Dec. 10, 1899. Albrecht : Odontol. Blatter, Apr., 1899. Blocli: Centralh. f. d. gesammte Therap., 1900, No. 1. Bauer: Oest.-Ungar. Vierteljahrs. f. Zalinlieilh., Apr., 1900. Zander : Deut. zahndrztl. Woch., 1900, No. 128. Vennerholm: Z. f. Tliiermedizin, 1900, 164. Schwarz: Centralh. f. Chir., 1901, No. 9, 248. Meyer: Med. Netus, Apr. 13, 1901. Neugebauer : Wien. Jclin. Woch., 1901, Nos. 50 and 52. The last three authors advocated the preparation for medullary anes- thesia by Bier's method. Kopfstein: Wien. Jclin. BundscJiau, 1901, No. 49, Saum: Deut. zalmdrztl. Woch., 1901, 156. Eeissenbach: Deut. zaJmdrztl. Ztg., 1901, No. 5. Bloch : Wien. zalmdrztl. Woch., 1901, Nos. 2 and 3. Deak: Magyar Fogaszati Szemle, 1901, No. 2. The last four authors imanimously praised the prompt anesthetic properties of the preparation in extractions of teeth. Annin: Wratsch, 1901, No. 11, 346. Annin used the preparation successfully in ophthalmic surgery, Schwarz: Milnch. med. Woch., 1902, No. 4. This author reported on over 100 cases of medullary analgesia by Tropacocain. Illing: J. Am. Med. Assn., 1901, No. 12. Neugebauer: Miinch. med. Woch., 1902, No. 44, 1862. Kozlowsky : Przeglad lekarsJci, 1902, No. 4. Kamann : Miinch. med. WocJi., May 20, 1902. Schleich: Deut. Klinik, 1902, 22. Mobilio: Arcliivio d'oftalmologia, Sept. and Oct., 1902. Fuchs-Golding : Zalmdrztl. Rundschau, 1902, No. 499. Vogt: Oest.-Ungar. Vierteljahrs. f. Zahnheil., 1902, No. 1. Loves: Die Zahnkunst, 1902, No. 26. The last three authors used the preparation with advantage in den- tistry, for the production of local anesthesia during extractions. Preindlsberger : Wiener med. Woch., 1903, No. 34. This author confirmed the observations recorded by Neugebauer and A LIST OF ANESTHETICS 835 others on the application of the preparation in the method of anesthesia of the spine. Bloch: Beut. med. Wocli., 1903, No. 24; Ver. Beil, 188. Triesch: Bericht iiber die 31. Hauptversammlung hessicher Zahn- drzte, 1902; Odontol Blatter, 1, Nos. 15-17. Triesch used 5 per cent injections of tropacocain in dentistry, heing thus able to induce a satisfactory anesthesia. He found that although the action of tropacocain was less prompt than that of cocain, it had the advantage over the latter in being less poisonous and dangerous. Eydygier: Przeglad leTcarshi, 1904, No. 7. This author reported on the success which attended the application of tropacocain as an anesthetic for the spinal cord by Kozlowski's method in 49 cases treated at the Lemberg Hospital. Stolz: Archiv f. Gyndkol., 73, No. 3. Stolz summarized the results of his large experience in connection with the anesthesia of the spinal cord as applied to gynecology and obstetrics. Bellandi : "L'Analgesie chirurgicale par voie rachidienne au moyen de la tropacocaine," Alexandrie, 1903. Levy: Deut. zdhndrztliche Woch., 1904, No. 18. Matthes: Ihid., 1904, No. 11. Preindlsberger : Yersammlung deut. Natur for seller und Aerzte in Meran, 1905; Allg. med. Zentral-Ztg., 1905, No. 42, 808; and Wiener klin. Woch., 1905, No. 26. Trautenroth: Deut. med. Woch., 1906, 253. The last two authors described tropacocain as preferable to stovain in connection with the anesthesia of the spine. Franceschi: Allg. med. Zentral-Ztg., 1905, No. 42, 809, and No. 43, 827. Klin.-therap. Woch., 1906, No. 41; Mwich. med. Woch., 1906, 1933. Koder: Wiener med. Woch., 1905, No. 37, 1781. Colombani : Wiener hlin. Woch., 1905, No. 21, 538. Foster: Beitr. zur Tclin. Chir., 1905, ^6, No. 1. Zahradnicky: Wiener med. Ztg., 1905, No. 5, 55. Karas: Wiener med. Woch., 1905, Nos. 20 and 21. Yolker: Monats. f. Gehurtshilfe und GyndTcol., 1905, No. 4; Miinch. med. Woch., 1905, No. 33, 1612. Eibolla: Stomatologia, 1905, No. 3. Eibolla secured excellent results by the use of tropacocain as a local anesthetic in dental operations. Becher: Dissertation, Giessen, 1905. Becher demonstrated the remarkable efficacy of tropacocain in medul- lary application to animals. 836 ANESTHESIA Slajmer: Wiener med. Presse, 1906, Nos. 22 and 23. This author was of the opinion that even anesthesia by inhalation could not compete with tropacocain anesthesia. His operations included 1,200 cases. Schwarz: Wiener Min. Wocli., 1906, No. 30; Presse med., 1906, No. 64. Arit: MilncJi. med. Woch., 1906, No. 34. Baisch : Deut. med. Woch., 1906, No. 38. Baisch combined tropacocain anesthesia with scopolamin-morphin hypnosis for gynecological operations, and the method was found to present various advantages. Miiller : Monats. f. Gehurtsliilfe und Gyndh., 1905, No. 2. Donitz: MiLnch. med. Wocli., 1906, No. 28. Kocher: Wiener med. Presse, 1906, 1039. Kiimmell: Med. KliniJc, 1906, No. 43, 1120. According to Kiimmell, tropacocain proved, in the Eppendorf Gen- eral Hospital of Hamburg, to be the best and the least poisonous, easy to sterilize, and a constant anesthetic. Bier (ibid.) expressed the opinion that the dangers of spinal anal- gesia were due to the selection of unsuitable drugs. In 1906, he an- nounced that he considered that tropacocain was the most suitable prepa- ration. Ach: MUnch. med. Woch., 1907, No. 33, 624. Ach described the results of lumbar anesthesia in 400 cases. He concluded that, of the drugs recommended for lumbar puncture, the least harmful, namely, tropacocain, should be selected. Thorbecke: Med. Klinih, 1907, No. 14, 386. Gallatia: Gynakol. Rundschau, 1907, No. 11. Bosse: Deut. med. Woch., 1907, No. 5. Goldschwend: Wiener Min. Woch., 1907, No. 37, 1098. This author had very satisfactory results with tropacocain, even in the most serious laparotomies. Masotti and Angeletti: Revista Veneta di scienze mediche, Jl{.7, Nos. 8 and 9; Deut. Med. Ztg., 1908, No. 14, 149. Eemenar: Wiener Min. Woch., 1907, No. 45, 1397. Gilmer: Miinch. med. Woch., 1907, No. 38, 1904. Baum: Ibid., 1905. Seitz: Ibid., 1905. Preindlsberger : Wiener Tclin. Rundschau, 1907, No. 46. Valenta : Gynakol. Rundschau, 1908, No. 1. The eight authors last mentioned gave favorable accounts of tropa- cocain and its lumbar use. Bloch: Heilhunde, 1906, No. 2. Bloch reported on the employment of tropacocain in general medi- A LIST OF ANESTHETICS 837 cal practice. He found it to be a never-failing remedy in ophthalmic and dental practice. Erhardt: Woch. f. Tierheilk., 1908, Nos. 27 and 28; Miinch. med. Woch., 1908, Nos. 19 and 26. Erhardt found that the addition of 3 per cent gum acacia to a 1 per cent solution of tropacocain diminished the toxicity of the anesthetic in lumbar anesthesia. See Erhardt' s Solutions. Donitz: Miinch. med. Woch., 1908, No. 32. Strauss: Med. Klinil, 1908, No. 6. Masotti and Angeletti: Revista Veneta di scienze mediche, 1908, No. 6. Saggini: Giornale di medicina militare, Apr., 1908. Hartleib : Miinch. med. Woch., 1908, No. 5. Valenta: Gynakol. Rundschau, 1908, No. 1. Eemenar: Wiener Min. Woch., 1908, No. 45. Tomaschewski : Deut. med. Woch., 1908, No. 51. Klein : Miinch. med. Woch., 1908, No. 47. The last eight contributions relate to the use of tropacocain in spinal anesthesia. Colombani : Wiener Jclin. Woch., 1909, No. 39, 1336. Colombani gave a detailed report of 1,100 cases of spinal anesthesia, showing that tropacocain afforded excellent results. Slajmer: Med. Blatter, 1909, No. 47. Eieck: Zentralh. f. Gynakol, 1909, No. 41, 1429. Klose and Vogt: Mitteil. aus den Grenzgehieten der Med. und Chir., 19, No. 5; Zentralh. f. innere Med., 1909, 965. The last paper was the result of an experimental investigation on spinal anesthesia. Heinz: Wiener med. Woch., 1910, No. 37. Slajmer: Beitr. zur Jclin. Chir., 1910, 67. Arlt: Miinch. med. Woch., 1910, No. 28. Morrison: Lancet, Sept. 10, 1910. The last four papers relate to lumbar anesthesia induced with tropa- cocain. Budde : Deut. militdrdrztl. Z., 1911, No. 4, 168. Gros: RiedeVs Mentor, 1911, 44. Tropein or Tropeine. — See Tropacocain. Turpentine. — Turpentine oil was proposed as an anesthetic by Nun- neley in 1849. It has been used in emergencies with success; it has also been added to chloroform to prevent collapse. Eichardson {Sci. Am. Suppl., No. 516, 8240) found that the vapor of turpentine was irritating at first and difficult to breathe, but that it was productive slowly of deep anesthesia, accompanied with convulsive rather than tetanic move- ments. Eecovery was slow, as if from deep intoxication. Eichardson 838 ANESTHESIA regarded its anesthetic value as indifferent. See Wachsmuth's Mixture, and also Apinol. TTdrenin. — A local anesthetic containing beta-eucain and adrenalin. According to "Riedel's Mentor," 1913, 308, ndrenin contains, per c. c, 0.01 gni. beta-encain hydrochlorid and 0.00003 gni. adrenalin hydro- chlorid iii physiological salt solution, with the addition of 0.5 per cent chloretone as a preservative. This combination is mentioned by Cob- lentz ("The Newer Eeniedies," 4th ed., 138), but he unmistakably refers to Eudrenin, q. v. Urea Hydrochlorid. — See Quinin and Urea Hydrochlorid and Thi- bault's Local Ana'sthetic. Urethane. — Urethane (Ethyl Carbamate; Ethylurethane), /NH2 C0< \OC2HB is well known as possessing a rapid hypnotic action, although not suffi- ciently powerful for use in cases where there is pain or distress. Hiib- ner and Sticker tried urethane on man, and Mairet and Combemale on animals, but were unable to show that it possessed a reliable hypnotic action, Nerking and Schiirmann {Med. Klinih, 1908, No. 46) subse- quently tested the preparation to ascertain its value as an anesthetic, assuming that urethane was split up in the organism into urea and the ethyl group. The intravenous application of 5 to 10 c. c. of a 30 per cent solution of urethane gave no positive result in rabbits, and it con- sequently seemed doubtful whether anesthesia could be obtained by the aid of urethane alone. Satisfactory results were obtained, however, with the combination of urethane and chloral hydrate. Nerking and Schiirmann used a 30 per cent solution of urethane and a solution of chloral hydrate 5:10, suitable doses being injected intravenously. These trials effected a quiet, safe anesthesia, with complete abolition of sensa- tion; but so far, to our knowledge, trials of this method have not been made on man. Hauckold {Z. f. exper. Path. u. Therap., 1910, 7, No. 3, 743) studied the effect of scopolamin on the action of urethane, and ascertained by experiments that scopolamin, which does not by itself produce anesthesia in rabbits, had a considerable effect in enhancing the anesthetic properties of urethane. Small quantities of urethane, which would not by themselves produce anesthesia, showed a narcotic action by means of a minimal dose of scopolamin. The latter was also found to possess a similar action in combination with morphin. TJrosemin. — This local anesthetic is a 1 per cent solution of uric acid in 3 c. c. of water, with the addition of 1 c. c. of Ensemin (q. v.), and 0.00005 gm. of adrenalin hydrochlorid. On urosemin, see Mannich and Schwedes: Apoth.-Ztg., 1913, 351; Wolfer: Med. Klinik, 1913, 1581. A LIST OF ANESTHETICS 839 Valerene. — See Amylene. Vanodrin. — This dental anesthetic contains 0.015 gm. novocain and 0.0001 gm. adrenalin liydrochlorid in 1 c. c. Vienna Anesthetic. — A mixture of alcohol, 13 parts by weight; chloroform, 77 parts by weight; and ether, 11 parts by weight. Vienna Elizabeth Hospital Mixture. — See Wertheim's Mixture. Vienna General Hospital Mixture. — Alcohol, 9 parts; chloroform, 30 parts ; and ether, 9 parts. On this mixture, see Potter : "Mat. Med. Pharm. and Therap.," 10th ed., 88. Vienna Mixture. — A mixture, introduced about 1856, of 8 parts of ether and 1 part of chloroform in hot weather; and 6 parts of ether and 3 parts of chloroform in cold weather. See Sci. Am. Suppl., No. 516; also, Eichardson: "Asclepiad," 1885, 274. According to Hewitt "Anassthetics and Their Administration," 3rd ed., '^^Q), Vienna mixture is composed of chloroform, 1 part, and ether, 3 parts. According to Miiller ("Narkologie," 492), Vienna mixture is composed of chloroform 3 parts and ether 1 part. Viferral. — See Polychloral. Vinyl Trichlorid. — See Ethylene (monochloro-) Chlorid. Vinyldiacetonalkamin. — Schering (Eng. Pat., 20,697, 1896) claimed that the vinyldiacetonalkamin of Fischer was a mixture of two bases, and that its derivatives might be employed as anesthetics. Wachsmuth's Mixture. — A mixture of chloroform, 4 parts, and oleum terebinth., 1 part. "To prevent syncope." Miiller, "Narkologie," 1, 493. See Turpentine, and cf. Apinol. Waite's lokaler Schmerztoter. — An anesthetic for minor operations, said to be a water solution of cocain, iodin, thymol, and glycerin, con- taining only cocain and creosote in glycerinized water (Gehe's Codex, Nov., 1910, 382). Water. — On water as a local anesthetic, see Wyeth : N. Y. Med. J., Jan. 6, 1906. Water has been employed as a local anesthetic (pressure anesthesia) in dentistry and in certain minor surgical cases. It is no doubt true that the anesthetic action of certain compounds is solely attributable to the pressure anesthesia produced by hypodermic injec- tion of the solution. Welt-Anaesthetikum (Universal Anesthetic). — A dental local anes- thetic containing adrenalin hydrochlorid, sodium chlorid, chloretone, cocain hydrochlorid, menthol, eucalyptol, and distilled water. Wertheim's Mixture. — This is a mixture of chloroform, 1 part; ethyl ether, 2 parts; and benzin or canadol, 1 part. It is a modification of Schleich's mixture and is often referred to as Vienna Elizabeth Hos- pital Mixture. Wertheim's solution or mixture was used by Williams {Trans. Soc. Anesth., ^ 98). Silk's experience {Hid., 5, 138) led him to believe that the petroleum ether contained in it was inoperative, so 840 ANESTHESIA that the solution was practically one of ether and chloroform. As such he considered that it had some merits. "Westron." — See TetracMorethane. Wigger's Anesthetic Ether. — See Ethyl Chlorid PolychI orated. Wilson's Local Anesthetic. — A water solution, of which 100 parts contain 7.5 per cent alcohol, 0.05 per cent boric acid, 0.05 per cent ben- zoic acid, 0.75 per cent cocain hydrochlorid, 1.0 per cent nitroglycerin solution (1:100), 0.05 per cent naphthol, and 2 drops of a mixture of equal parts of oils of eucalyptus, peppermint, gaultheria, and thyme. Yohimbin. — This is claimed to be a local anesthetic for eye and nose practice. It is, however, best known as an aphrodisiac. Yohimbin hydrochlorid (CaaHggOsHo.HCl) is a white crystalline powder, having a melting point of + 288-290° C. For a full study of the pharmaco- dynamic properties of yohimbin, see Mtiller : Archives internat. d. phar~ macol. et d. therap., 1907, 65; Archiv f. Anat. und Physiol.^ 1907, 391; Franz: Med. Klinih, 1907, No. 34, 1027. Miiller showed that the action of yohimbin depended chiefly on its influence on the walls of the ves- sels, and that, even when applied locally, the action was vasodilating and anesthetic. Large doses were found to produce a continued fall of blood pressure, and lethal ones to paralyze the heart also by injuring the cardiac muscle. Holterbach (Berl. tierdrztl. Woch., 1907, No. 32 ; Beut. tierdrztl. Woch., 1907, Nos. 13 and 14) points out that the anes- thetic action of yohimbin may be said to be recognized. On the com- parative effects of yohimbin, protoveratrin, and veratrin on isolated muscle and nerve, see Waller: Proc. Physiol. Soc, 1910, xi-xiv; J. Phy- siol., 41, xi. On the anesthetic action of yohimbin, see the following papers : Lowy and Miiller : "Zur Kenntnis der anasthesierenden Wirkung des Yohimbin," Miinch. med. Woch., 1903, No. 15. Magnani: "Zur anasthesierenden Wirkung des Yohimbin," ibid., 1903, No. 5. Magnani: "Un nuovo alcaloide anestetizzante la congiunctiva e la cornea," La clinica moderna, 1902, No. 35. Oberwarth : "Ueber Yohimbin," Virchows Archiv, 153, 292. Yohydrol. — "Yohydrol" is a proprietary name for a Yohimbin Hy- drochlorid {q. V.) of German manufacture. Zeuner's Halspastillen ; Zeuner's Hustenpastillen. These contain Anesthesin (q. v.). Zykloform. — See Cycloform. CHAPTER XXI STATISTICS Introduction, Collateral Information : Local Anesthesia ; Nitrous Oxid Alone or with Air; Nitrous Oxid with Oxygen; Anesthol-Ether Sequence; Chloroform-Ether Sequence; Nitrous Oxid-Ether Sequence; Anesthol; Ether, Drop or Vapor; Ethyl Chlorid-Ether Sequence; Ethyl Chlorid; Chloroform-Oxygen; Chloroform, Drop or Vapor; Intratracheal Anes- thesia ; Oil of Bitter Orange Peel-Ether Sequence ; Comparison of Amer- ican Statistics for 1905-1911' with Those for 1892 ; Comparison of Amer- ican with European Statistics; American Statistics, 1905-1912, Inc. Conclusions. INTRODUCTION In March of 1911, circulars were sent out to all the puhlic hospitals with not less than ten beds in the United States, Canada, Cuba, and the Canal Zone. Ninety-nine hospitals, widely separated (in forty States, Canada, and the Canal Zone), furnished the facts on which these statistics are based. The data given by these ninety-nine hospitals may be considered as fairly representative of statistics from American hospitals in general. In New York City two large hospitals (St. Luke's Hospital and the German Hospital) had statistics from an anesthetic standpoint immediately available. We feel that hospital administration should require that accurate data as to the anesthetics used should be kept on file, as well as other information. The Army and Navy officials sent replies by return mail, showing that these statistics are kept on file as are others. A careful study of the Army and Navy statistics will amply repay one. (Page 842.) It is a remarkable fact that the only two fatalities that occurred in the naval service were under ether. The location of the four chloroform fatalities mentioned in Table 2 is unknown. The third table on page 843 includes the Army and Navy statistics. The anesthetics are placed according to their value as regards life. The 841 842 ANESTHESIA TABLE 1.— The United States Navy for the Years 1908-1910 Anesthetic Ether Ether (rectal) Ether, morphin and scopolamin Ether and nitrous oxid Ether and chloroform Ethyl chlorid (general) Ethyl chlorid and ether Ethyl chlorid and chloroform. . Chloroform Cocain Cocain and ethyl chlorid (local) Cocain and epinephrin Beta-eucain and epinephrin Eucain Novocain Novocain and epinephrin Schleich's solution No. 2 Total Number 2,218 2 40 140 2 16 24 2 365 91 3 3 4 1 4 4 2 2,921 Deaths TABLE 2. — Anesthetics Used in Surgical Operations Performed on Officers and Enlisted Men of the Army for the Years 1904-1910 Year Chloro- form No. Ether No. Chloroform and Ether No. Spinal No. ^ Local No. 1904 835 713 684 571 497 335 296 878 806 861 831 965 1,326 1,513 "83 73 37 67 100 55 "eo "29 9 1,096 1905 1,070 1906 1,234 1907 1,270 1908 1,652 1909 1,873 1910 1,793 Total 3,931 7,180 415 98 9,988 ^ The agents used in spinal analgesia were tropacocain and beta eucain. Four deaths were due to the anesthetic (chloroform) in all the cases. number to the left of each anesthetic refers to the relative frequency of their administration. These statistics speak for themselves. The following remarks are based upon collateral information obtained with the numerical data. The total number of administrations from the ninety-nine hospitals was 278,945. Ph ooicN.iOT-ii-(cocO'*oici-*'0'-Ht>.ofco5t^ioa5fo>-H05oo»^'^o t^00{MOc0(N»0(Mi-HO0302'*-O.— ii— (fCfO'*0'OTt0 CD O • • ■ O CX) CO • • OfOai(MlMr-|..-T-H •• cffo" : : : ; ; . . . . O r— ( l>.iOO'-l(MOO'^OiOO GO 00 t- GO —1 !>• (M 05 I- O CO^C0_^-* 05_0 CO CJ^OI 1-1 O co'oT cc'i-T i-T r-T O o ^0(McD -COOlOOCft -CDCdN-^TiH 1—1 CO t> CO -cocoes • y-l i-l (M rtiCOOOiOiOOOcO— I loco r-< Cl'*ClC5C5'-iOGOCft Clt^GC^t^CO^OJCt 0_C^_^t> O^GO ^ '^j-' '-' ci^-^it^o^t^r^co cooooooi-^coc^coi-H ^H>— IrHC^r^-COOiCDO ^Cir^c^t^t^coi-ico COC2ClC0Tt— I 05 0t^cO-*t^-*iMCO t^TlCOl^iCGO CO LO GO C5 1-1 ^ lO be Qj b:S at," f< -*J CO -^ O jc o3 fiil'i O -^ fl -l^L^H o3 m-STh 03 OJ oj O — ,-C 2 cc c - cc ■^ L. >^ S 1* ■S a3 " s^ c " ^ i _ z ■ ■ ' ^043 cnoic^cocRi— loOi— I lOiOCOClOiO-^i-i tn bC 2 fl S >^ '^ - 0) 0) o H 1=1 (3 >2 (3 a o o o =^ t^ 03i0C0'-iOC"|(M'-HC0OOC1Ci-tCO'-ICOIO CDcoTtiOC01>.05»0 OiCOGOCOiOr-iCOt- (NOC'*O0CO00i-(^ OTtl:^c0 lOGO'-iC^iM'-iOOOOCiiMO^ O CO >0 »C TJH CO lO O l> IC CO ■* OGOi-H|>--^0>— I CO. CO (M lO • -(MCO OCO • • • lOO (N ^ • • -.-KM CO i^ 05 cft CD »0 1— I lO C0 1-1 CO lo t-GOCO^t^C-lOiC^Ol^O t-KMt-iOCOiOCOcOOC^OI ,-H> O lO ■* Ol l> cot^t^cD^^'-|<^^(^J'*^-H050 -H01>'*0'*'#0-* t^(MCOl>OiOO i-H thcoco <-i coco ^ 1002CO'HO-*1^00 t^coiot^i— icot>o GO 05 (M IxN '^ (M Ol-^ OCO Ci Oi t^ o Oi O "-H "* OOCO(MTt0 tH 1— I (M (M CO 1-1 iC CTl CI ^ ClCOO'^CftOilMiO t^ rH CI ^ O -H TfH o a o ow CO O ^ ;*^ ,S CO - 1^ fl o^'« •t; „^ «^ »3 b -^ -^ T! HO X . . O ^ 'O'O 02^ ^-C c o !B 03 y o 2 =»' -^HTt* CO I Oh I I I I I I I I I I I I I I I OOOOOOO OOOOOOOO OOOOOOO OOOOOOOO t^ t^ lO T-1 t^ -^ O 1-H o o> ro (M >— 1 1— I <— I cx) CO 1^ -* CO CO fo ir^ (M T— 1 1— I ■* t^ O • -OO i-H • (N T-I(M r-l 1-1 1— I CO O (M • • C=' o o STATISTICS 857 CONCLUSIONS The statistical tables coincide remarkably with the principles advo- cated in these different chapters. Bearing in mind the pharmacological action and clinical history of each anesthetic as well as the statistical tables, we make the following deductions and recommendations : (1) Nitrous oxid with oxygen (with or without ether) is the safest inhalation anesthetic we know of at present; (a) Kitrous oxid should not be used alone; (b) Nitrous oxid should not be used with air, if oxy- gen is available; (c) The nitrous oxid-oxy gen-ether sequence is safer than the nitrous oxid-ether sequence; (d) The statistics bear out the principles given in Chapter II concerning oxygen as a factor of safety. (3) Anesthol alone should not be used. A study of the tables will show that a steady decrease in the use of this agent alone has taken place since 1908. (a) Anesthol as a preliminary to ether gives a safe se- quence, and has steadily increased in favor from 1905 to the present time; (b) The combination of anesthol and chloroform has steadily de- creased in use, showing that it is unsatisfactory; (c) Anesthol, alone or with any other agent, should not be given by the closed method. (3) Ethyl chlorid should not be used as a terminal anesthetic on account of its physiological action. It is not safe, according to these statistics, as a preliminary to chloroform, nitrous oxid, or anesthol. (4) Chloroform alone should not be used except in emergencies, or in cases in which it is specially indicated. Its use has steadily decreased from 1905 to the present time, (a) The chloroform-ether sequence, as shown by the table, is relatively safe, ranking higher than the nitrous oxid-ether sequence, or ether alone; (b) As the majority of the hospitals of the United States use preliminary medication, we may conclude that this factor of safety has been employed when the chloroform-ether se- quence was used; (c) The combination of chloroform and oxygen, ac- cording to these statistics, is safer than ether alone. (5) Ether alone is more generally used, according to these statistics, than any other agent, combination, or sequence, comprising nearly half of the 488,000 administrations reported, (a) Ether alone is not as safe as is generally believed; (b) Ether is materially safeguarded by oxy- gen; (c) Chloroform-ether, nitrous oxid-ether, and anesthol-ether are relatively safe sequences, ether being the terminal anesthetic. (6) Sequences and combinations, when properly used, are safer than any known single anesthetic. APPENDIX I^ ETHYL ETHER History of Ethyl Ether. Manufacture of Ether : Ether from "Methylated" Alcohol ; Ether from Ethylene; Theories of Etherification. Purity of Ether: The Commercial Purification of Ether; Veri- fied Tests for Proving Purity of Anesthetic Ether; Role of Water in Anesthetic Ether ; Explanation of Changes Liable to Occur in Ether Im- properly Stored; The Purification of Ether Eemnants with the View of Eemoving Aldehyd in Particular; Acidity of Ether and Effect Thereon of the Container; Physiological Consideration in Eeference to Small Amounts of Impurities; The Degrees of Purity of American Ethyl Ethers Used for Anesthesia. HISTOEY OF ETHYL ETHER Eaymundus Lullius," in the thirteenth century, and Basilius Valen- tinus,^ in the fifteenth century, investigated the action of sulphuric acid upon spirit of wine, and consequently it is possible that these alchemists were acquainted with ethyl ether.* It is to Valerius Cordus, however, that we owe our first exact knowledge of the existence of the compound.® The process of Cordus for the preparation of ethyl ether was published by Conrad Gessner in 1552/ and it occurs in the later editions of the first legal pharmacopoeia of Germany.'^ ^ Much of this appendix is taken from a paper by Baskerville and Hamor, J. Ind. Eng. Chem., 3, Nos. 5 and 6. -"Epistola accurtationis lapidis benedicti; libelli aliquot chemici, " 1600, 319. ^ This alchemist refers to a spirit obtained in this way which has a ' ' subtle, penetrating, pleasant taste, and an agreeable smell." See Kopp's "Geschichte der Chimie," 1847, 4, 299. * This is, in fact, generally assumed, and one would be inclined to accept it as correct, were the authenticity of their writings established. ° "Dispensatorium pharmacorum omnium," 1535. •^ ' ' Thesauro Euonymi de remediis secretis, ' ' 1552. ' This recipe is as follows : Equal parts of spirit of wine which has been rec- tified three times and sulphuric acid are allowed to remain in contact for two months, and then the mixture is distilled from a water- or sand-bath; the distil- late consists of two layers of liquid, of which the upper one is the oleum vitrioli dulce verum. 858 APPENDIX I 859 Ether is mentioned by Libavius/ Oswald Cross,^ and Willis;" but at the commencement of the eighteenth century, the details of its prep- aration seem to have been almost entirely lost, even though a mixture of spirit of wine and ethyl ether was employed in medicine art this period. This mixture was, however, introduced into commerce by Martmeyer, an apothecary of Halle, under the name of Panacea vitrioli. It was recommended by Friedrich Hoffmann, and under the name of Liquor anodynus Hoffmani, or Hoffman sche Tropfen, it became well known, but the preparation of this medicine was kept secret for a considerable period, and the positive presence of ethyl ether — for that matter, its existence — was not demonstrated until it was first prepared "free from spirit of wine." In 1730 August Siegmund Frobenius * described, in general terms, the preparation of spiritus vini cetliereus, but without publishing any details.^ On November 18, 1731, Frobenius made experiments with ether and phosphorus before a meeting of the Eoyal Society,*^ and in his second contribution to the Eoyal Society he gave his method for the preparation of ether in more detail, but this description was not made public until after his death in 1741, when a detailed receipt was pub- lished by the secretary.'^ The method of Frobenius was soon widely adopted, and several Ger- ^"Alchemia," 1595. ^ ' ' Basilica chymiea, ' ' 1608. ^ ' ' Pharmaeeutice rationalis, ' ' 1675. "■FMl. Trans., 36, 283. '^ He manufactured, the ether in Hanckewitz 's laboratory and sold it at a high profit. He forwarded some of the new substance to St. F. Geoffroy, and wrote (1730) as follows, after extolling the valuable properties of the compound: " Paratur ex sale violatili urinoso, plantarum phlo^isto, aceto valde subtili, per summam fermentationem cunctis subtilissime resolutis et unitis. " "See Mortimer: Ihid., Abst., 9, 372. ''Phil. Trans., Abridg., 9, 380. This may be thus stated in abstract: "Take 4 lbs. in weight of the best oil of vitriol, and as much in weight of the best alcohol, or the highest rectified spirit of wine. . . . First, pour the alcohol into a chosen glass retort, then pour in, little by little, one ounce of oil of vitriol; then shake the retort till the two liquors are thoroughly mixed, when the retort will begin to grow warm; then pour in more of the spirit of vitriol, and shake it again." The mixture was then placed on a sand bath, and gradualy heated, "that the drops may fall so fast that you may count five or six between each . . . continue this heat as long as they emit the scent of true marjoram. As soon as the smell changes to an acid . . . take out the fire. . . . There remains be- hind an eleum vini. . . . The second day, when your glass is cold, infuse the remainder with half as much alcohol, and distil again as before, and you will have the same; the third day again with as much, and proceed as at first, it gives it again. Go on as long as you can obtain any (of the ethereal spirit) till all turns to a carho ; then separate it, and alcalize it with spirits of salt armonioB made without spirits of wine, till all effervescence ceases, and distil once more e Balneo Marice ; so is it ready for experiments." 860 ANESTHESIA man and French chemists studied the preparation of ethyl ether. In 1757 Antoine Baume published his "Dissertation sur Vcetlier," in the first 26 pages of which he gave an historical discourse on cether vitrio- lique. On account of its inflammability ethyl ether was termed at this time naphtha^ but was also called "vitriolic ether," "sulphuric ether," and "vitriol-naphtha," since it was prepared by the action of sulphuric acid on alcohol. MANUFACTURE OF ETHER Valentin Eose,^ in the year 1800, demonstrated that the name "sulphuric ether" was a misleading one, since this substance, when pure, does not contain any sulphur or sulphuric acid. Pourcroy^ propounded the idea that ether is formed from alcohol by the with- drawal of the elements of water. However, a number of facts con- tradicted this view; for example, Frobenius had observed that the residue in the preparation of ether may again be employed for a future conversion of alcohol into ether, a fact which had met with confirma- tion in. the hands of other chemists, particularly Cadet (1774).^ The discovery of the continuous process now employed for the manu- facture of ether is generally attributed to Boullay. * Squibb ^ stated that 360 pounds of concentrated sulphuric acid sufficed to etherify 130 bar- rels of clean spirit; the acid charge must be then changed, as the mix- ture will have become dark and tarry, and liable to froth in the still.*' Ethyl ether was first manufactured on a large scale in this country ^Allg. J. Chem. (Scheerer), 4, 253. This savant in conjunction with Vauquelin [Allg. J. Chem. (Scherer), 6, 439] made attempts to experimentally establish this view, the results of which were confirmed in 1807 by Saussure and in 1815 by Gay-Lussac,- both of whom analyzed ether. Then it was thought that the action of sulphuric acid on alcohol could be accounted for by the fact that this acid removed from the alcohol either the ele- ments of water or water already present in the compound. ^ Mements d'Mstoire naturelle et de cMmie, 1789. ^ Cadet and Baume had a discussion concerning the manufacture of ether; and the former stated that, while Baume sold the compound at twelve livres per ounce, he charged only forty sous for the same quantity. Quite pure ether was prepared by Lowitz in 1796 by means of chlorid of lime ( ?) (J. Pharm. CMm., 1, 97). * This process depends on the fact that a small quantity of sulphuric acid is sufficient to convert a large quantity of alcohol into ether; in fact, theoretically, one portion of sulphuric acid will convert an unlimited quantity of alcohol into ether, but in practice some of the sulphuric acid is reduced, and not only is there loss of acid and alcohol, but, in consequence of this reduction, the ether becomes contaminated with sulphur dioxid and must be purified before use. ^ " Ephemeris, " 2, 590. *See TJ. S. Patent 516, 766, of 1894, of Kraft and Eoos. The production of sulphur dioxid in the process may be prevented, it is claimed, by using benzene- sulphonic acid in the place of sulphuric acid in the still. APPENDIX I 861 by Eosengarten & Sons at Philadelphia in 1823, and oy Carter and Scattergood of the same city in 1834. Ether from "Methylated" Alcohol. — One of the strong arguments in advocating the enactment of denatured alcohol laws was cheaper ethyl alcohol for the manufacture of ether. Ethyl alcohol denatured with ten per cent methyl (wood) alcohol was first authorized. "Methylated" alcohol was then used for the manufacture of ethyl ether. Ether made from methylated spirit contains, according to some authorities, a con- siderable quantity of gaseous methylic ether in solution, which lowers the specific gravity and boiling point of the preparation.^ Ten per cent of methylated ether may be detected by the mixture commencing to boil at a lower temperature than ether prepared from rectified spirit." Three grades of ether prepared from methylated spirit are used in Great Britain.^ Hewitt * states that, while it may be regarded as ^Abraham: Chem. and Drug., 41, 520. ^ Jones (Pharm J. and Trails., 16, 663) obtained the following results with various British ethers: 100 c.c. tahen. c.c. obtained. Bemarks. Eect. ether, 0.720 Kect. ether, 0.730 Meth. ether, 0.717 60 Boiled freely at 74° F. Meth. ether, 0.720 54 Meth. ether, 0.730 23 * Allen ["Commercial Organic Analysis," 1908, 1, 181] has pointed out that, owing to the extreme volatility of methylic ether, ether made from methylated spirit would be practically pure ethyl ether, were it not for the presence in it of other constituents of wood spirit. This is undoubtedly true from a general stand- point, but nevertheless methylic ether has usually been considered to exist in solu- tion in ether prepared from methylated spirit, as determined by an observation of the commencement of boiling. Williamson (Ann., 81, 79 ; see also Norton and Prescott: Am. Chem. J., 6, 244) found that methyl ethyl ether is formed together with methyl ' and ethyl ethers by the etherification of a mixture of methyl and ethyl alcohols by sulphuric acid ; and since methyl ether boils at 34° C, and methyl-ethyl ether between 10° C. and 13° C, the latter is likely to occur 'in larger amounts than the former in ether prepared from methylated spirit. Ether of the specific gravity 0.735 has been oflficial in Great Britain for many years, but foreign pharmacopoeias only recognize the fluid which is official in the British Pharmacopoeia as "^ther Purificatus. " The latter is identical with the "uEther pro narcosi" of the German and Swedish Pharmacopoeias. In 1893 Dott (Pharm. J. and Trans., 23, 617) suggested that the specific gravity of the official ether of the British Pharmacopoeia should be altered to "not exceeding 0.724." The following ethers are used in Great Britain: (1) From Pure Eecti- fied Spirit: (a) aether (off.). Sp. gr., 0.735. "Ordinary medicinal ether." Occasionally employed as an anesthetic, but is not so suitable for inhalation as (b) "ajther purificatus" (off). Sp. gr., 0.720-0.722 (British Pharmacopoeia, 1898, 26): (2) from Methylated Spirit: (c) "absolute ether." Sp. gr., 0.717- 0.719. Said to be not adapted for general anesthesia; (d) "rectified ether." Sp. gr., 0.720. Reported as being adapted for producing general anesthesia; (e) "methylated ether." Sp. gr,, 0.730. Employed for common purposes. * ' ' Anaesthetics and Their Administration, ' ' 1907, 22. 862 ANESTHESIA hi.r;-hly probable that the purer ether possesses slight advantages over the methylated, the latter, if carefully prepared by a recognized manufac- turer, is certainly quite suitable for hospital use. Eichardson ^ decided in favor of "methylic ether" for rapid anesthesia. Ethers on the American market — that is, those manufactured in the United States from rectified spirit or from denaturant formulas authorized by the Commissioner of Internal Eevenue ^ — are, so far as we have been able to ascertain, free from methylic ether, methyl-ethyl ether; and American ethers are not contaminated with these substances, formaldehyd, or formic acid. Ether from Ethylene. — Fritsche ^ devised a method for the prepara- tion of ether free from alcohol. In this method, gas containing ethylen is treated with sulphuric acid,^ and the ethyl-sulphuric acid so obtained is converted into ether and sulphuric acid by means of water. This process was operated on a commercial scale in this country for some time,^ but the industry was finally destroyed by the Denatured Alcohol Act. Theories of Etherification. — Mitscherlich " proposed the "catalytic hypothesis"' to account for the action of sulphuric acid on alcohol, and Berzelius adhered to the same view. Neither of these chemists noted, however, that the first action of sulphuric acid on alcohol, in the manu- facture of ether, is the production of "sulphovinic acid," or hydrogen ethyl sulphate, an observation which was made by Hennell. This sub- ject was investigated quite carefully by Liebig.'^ He concluded that ethyl sulphuric ether was first formed, and that this decomposed at a temperature of -|- 126° C. to -|- 140° C. into ether, sulphuric acid, and sulphur trioxid, this latter combining instantly with the water formed in the reaction; the sulphuric acid again formed ethyl sulphuric acid "■Med. Times and Gas., April 9, 1870. - Alcohol to be used in the manufacture of ether in the United States may be denatured with ether. See Eegulations No. 30, Supplement No. 1, United States Internal Eevenue; and Bulletin No. 130, Bureau of Chemistry, 1910, 163. ^ Chem. Ztg., 33, 759. See also Pierre : Ann. chim. phys., IS, No. 3, 360, 400. *Z. anal Chem. 36, 298; U. S. Patent No. 475,640, Jan. 19, 1897. ^ Bull. 92, U. S. Dept. of Commerce and Labor, Bureau of the Census, 1909, 96. Vaporized petroleum was used as a source of ethylene, and natural gas was sug- gested later, but it was not available in the locality of the plant and it was not considered economical to move the plant. Monroe proposed erecting a by-product coke plant at the locality, since this furnishes comparatively large amounts of ethylene, but such a step was not taken owing to the inability to secure encour- agement from the firm controlling the most suitable by-product coke oven. It is likely, however, that a similar industry may be revived, as natural gas might serve as a suitable material from which to prepare ether (cf. French Patent, 352,687, of 1905, of Lance and Elworthy). "Pogg. Ann., 31, 273; 53, 95; 55, 209. ''Ann., 23, 39; SO, 129; QO, 31. APPENDIX I 863 with the alcohol, which was being continuany added, and thus Licjbig accounted for the continuous nature of the reaction.^ Williamson ^ adopted the views of Laurent and (Jerhardt, and there- fore gave ethyl ether the molecular formula CjH^oO, whereas those using the equivalent weights adopted the formula C4H5O. However, accord- ing to the theory of types, alcohol is derived from water by the replace- ment in it of one atom of hydrogen by ethyl, and hence ether, accord- ing to Williamson's view, must be regarded as alcohol, in which the hy- drogen of hydroxyl is replaced by ethyl. By a new synthesis he was enabled to prove the correctness of this conception, not only for etliyl ether, but for ethers in general. His method was the transposition taking place between sodium ethylate (JSTaOCoHg) and ethyl iodid (CoHgl) ; and the formation of ethyl ether from alcohol and sulphuric acid Williamson explained by a continuous breaking down and reforma- tion of ethyl sulphuric acid, made possible by the contact of alcohol with the acid at + 140° C. Further confirmation of the views of Williamson was afterward given by Berthelot.^ Chancel,* who really preceded Williamson in pub- lication, independently arrived at the same conclusions, by heating a mixture of potassium ethyl sulphate and potassium ethylate. The ob- jection that ethyl ether, because of its low boiling point, could not con- tain the double number of carbon atoms in its molecule Chancel re- moved by citing the boiling point of ethyl acetic ester. 1 The simultaneous production of water and of anhydrous sulphuric acid was accounted for by the assumption that the latter only combined with the water in its immediate neighborhood, while, in the other parts of the mixture, the passage of the ether vapor carried away some water vapor. Heinrich Eose explained the curious fact that ethyl sulphuric acid should be formed and decomposed at the same time and in the same liquid by the suggestion that a diminution of tem- perature sufficient to permit of the formation of ethyl sulphuric acid occurred at the point where the alcohol flowed in, but that the other portions of the mixture were sufficiently hot to result in the decomposition of this acid. Mitscherlich rendered this hypothesis untenable (J. Cliem. Soc, 3, 24), by demonstrating the continuous formation of ether under conditions in which no such local diminution of temperature could occur. Graham, like Mitscherlich and Berzelius, assumed the existence of contact action, but shortly afterwards the investigations of Wil- liamson placed the true theory of the continuous etherification process on an ex- perimental basis. Prior to his work no completely satisfactory theory of the formation of ether could be established, due to the lack of complete experi- mental evidence and owing to the general use of the equivalent weights. 2 Brit. Assn. Repts., 1850, 65; Phil. Mag., 37, No. 3, 350, 3 J. Pharm., 26, No. 3, 25. 4 Compt. rend., 6, 369. 864 ANESTHESIA PURITY OF ETHER The Commercial Purification of Ether. — The ether distillate re- sulting from the reaction between sulphuric acid and alcohol is usually treated with either milk of lime or sodium hydroxid, to remove the sul- phur dioxid and to absorb any "oil of wine," ^ and then further recti- fied.2 The rectified ether is usually run into tin cans provided with a neck and the cap is sealed by soldering.^ Verified Tests for Proving Purity of Anesthetic Ether. — Specific Gravity of Anesthetic Ether. — The specific gravity of ether in- tended for anesthesia should not exceed 0.720 at 15° C, providing an ether containing minimum quantities of alcohol and moisture is required ; however, an ether which shows a specific gravity of 0.7215 (2 per cent absolute alcohol), 0.7228 (3 per cent absolute alcohol), or even 0.724 (4 per cent absolute alcohol), providing the sole "impurity" is ethyl alcohol, is acceptable for anesthetic purposes, according to various phar- macopoeias. The specific gravity may be best determined by means of a pyknometer. A convenient form of pyknometer is that devised by Squibb * and also described by Eosengarten,^ the use of which is described on page 865. Boiling Point. — The fractionation should show that at least 97 per coDit of the sample distils over between -|- 34° C. and -\- 36° C. (at 760 ^ The term ' ' heavy oil of wine ' ' is held to signify the oil which passes over if the temperature is raised after the preparation of ethyl ether. Liebig (Handw. d. Chem., 3857, I, 223), who found that it passes over when sulphur dioxid and olefiant gas are given off, regarded ' ' heavy oil of wine " as an ethyl sulphate of "etherol. " According to Claesson (J. praM. Chem., 19, II, 259) and SeruUas {Ann. chim. phys., 39, II, 152) it consists of ethyl sulphate mixed with olefines. The composition varies materially, and the phrase is indefinite and rather vague; but it is considered that the yellowish oil of a penetrating odor (sp. gr., 1.095 to 1.13) procurable in the manufacture of ethyl ether is a possible contaminant of the latter, and the term ' ' heavy oil of wine ' ' is therefore used by way of dis- tinction. ^ In rectification the apparatus devised by Mohr has had extensive use. This consists essentially of a still from which the vapor is conducted through a vessel kept at + 35° C. by warm water. Here most of the alcohol and water vapors are condensed and the ether passes over to be condensed in a suitable, well-cooled worm. ^ It sometimes happens that a small amount of zinc chlorid, used as a flux in soldering ether ' ' tins ' ' by manufacturers, is introduced accidentally into the ether. This constitutes one of the real difficulties in being sure that an unopened tin of ether is uncontaminated. 4 " Ephemeris, " 1897, 1773. 5 J. Ind. Eng. Chem., 1911, 3, No. 11. APPENDIX I 865 mm.), and none of it should come over above -)- 37° C. ;^ after the fractionation to this temperature no residue should remain in the frac- tionating vessel. Eesidub (Extractive MatteK;, Odok, and Acidity). — (1) When Fig. 283. — A Calibrated Pyknometer of 25 c. c. Capacity. To determine its volume the pyknometer is first weighed with water at 25° C, choosing a convenient mark on the stem, say 30 or 40, whichever may be more convenient, as indicated in the sketch by a line. The pyknometer is then filled with ether to a little above the mark at which the weight of water has been determined and placed in a 1,000 c. c. beaker containing water which is carefully kept at 25° C. and constantly stirred with a ther- mometer. When the volume of ether becomes constant in the pyknometer, the excess of ether is drawn off by means of a capillary pipette until the desired mark is exactly reached. The pyknometer is then quickly dried with filter paper and weighed. A capillary pipette for this purpose is easily made by drawing out an ordinary eye- dropper. 25 c. c. of the sample are allowed to evaporate spontaneously in a clean, dry glass dish, the moist residue must possess no odor, and must neitiier ^ Although the boiling-point of pure ether is + 34.6° C. at 760 mm., there are no ethers of anesthetic grade on the market which comply fully with this require- ment, owing to the mutually opposing influence of water and alcohol on the boiling point, and only ether distilled over sodium closely approximates it. Since, there- fore, these influences render the constancy of the boiling point as ordinarily de- termined of little or no use as a criterion of purity, it is suflScient to require that ether shall commence to distil at a temperature not under + 34° C, and that it shall possess a boiling point of + 34°-36° C. 866 ANESTHESIA redden nor bleach blue litmus paper; this residue must evaporate com- pletely on a water bath, that is, there should be no fixed residue. (3) 100 c. c. of the ether under examination are allowed to evapo- rate spontaneously in a flask until about 15 c. c, remain in the vessel. This residue should be free from color and foreign odor, and should comply in full with the following tests : (a) When 5 c. c. are allowed to evaporate at room temperature after the addition of 2 c. c. of water, the residue should neither redden nor bleach sensitive light-blue litmus paper. (b) When another portion of 5 c. c. is allowed to evaporate on a 9 cm. filter paper contained in a porcelain dish, no foreign odor (amyl compounds, empyreumata, pungent matters, etc.) should be perceptible as the last portions disappear from the paper, and the latter should be left odorless. The ether should be added to the paper in portions in such a manner as to completely moisten it each time. (c) On the addition of the remaining 5 c. c. to 5 c. c. of concen- trated sulphuric acid, kept cool during the test and contained in a glass- stoppered tube previously rinsed with concentrated sulphuric acid, there should result no perceptible coloration. Anesthetic ether should comply in full with these tests. Acidity. — When 20 c. c. of pure ether are shaken with 10 c. c. of pure water and 2 drops of phenolphthalein, the same depth of color should result on adding an equal amount of IST/lOO potassium hydroxid solution as in a test using pure water alone.^ When more than 1 c. c. is required the ether should be rejected for anesthetic purposes. AcETALDEHYD. — On covering solid potassium hydroxid (two clean, freshly broken pieces about 2 cm. long will answer) with 40 c. c. of the same in a 50 c. c. glass-stoppered vessel and allowing this to stand for three hours, tightly closed and protected from the light, and shaking occasionally, the potassium hydroxid should not acquire a yellowish color, and no yellowish or brown-colored substance should separate. This is recommended as the exclusion test for anesthetic ether.^ ^When 0.5 c. c. of a 1: 100 alcoholic solution of phenolphthalein is added to 100 c. c. of water, 0.5 c. c. of N/100 KOH is necessary to produce a distinct red color. In this connection see Trommsdorff 's table in Bockman's " Chemisch-tech- nische Untersuchungsmethoden der Grossindustrie, " 3rd ed. ; Cohn's "Indicators and Test Papers," 220; and A. A. Noyes: J. Am. Chem. Soc, 32, 815. It ap- peared from the last mentioned investigation that thymolphthalein might be ad- vantageously substituted for phenolphthalein as the indicator in estimating the acidity of ether. It was found, however, that, when the former is employed, the color change is less distinct, and that it is less sensitive. ^ In order to determine the value of this test experimentally, 5 gm. of potassium hydroxid were added to the following samples of ether, 30 c. c. of each being used in the tests: (1) Ether distilled over sodium, and containing mere traces of acetaldehyd; (2) an ether containing 0.5 per cent of hydrogen dioxid but otherwise pure; APPENDIX I 867 Peroxids. — When 2 c. c. of a 10 per cent cadmium-potassium iodid solution are well shaken with 10 c. c. of the sample there should result no liberation of iodin within one hour. This may be easily determined by adding starch solution, although the yellow color which results in the presence of the merest traces of peroxids is easy to distinguish. Role of Water in Anesthetic Ether. — The presence of excess mois- ture should be guarded against in the storage of ether, since ether in contact with water or moist air for any length of time gives rise to vari- ous impurities of an objectionable nature. Thus anesthetic ether may develop impurities to be avoided quite as much as if they had been in- troduced in the original materials or later produced in the manufacture or unintentionally added in the preparation for distribution in com- merce. Ether, when freshly distilled over sodium, possesses a specific gravity of 0.7178 to 0.719 at 15V4° C; but if it is not, immediately after its rectification, drawn ofi' into vessels, which are at once sealed and care- fully stored, the specific gravity increases in a short time. The purest ether procurable on the market is of 0.718-0.719 specific gravity at (3) an ether intended for analytical purposes; this ether contained small amounts of the moisture; (4) No. 3 after the addition of 3 per cent of absolute alcohol; (5) No. 3 after the addition of 0.05 per cent of acetaldehyd; (6) No. 1 after the addition of 0.05 per cent of acetaldehyd; (7) No. 3 after the addition of 0.05 per cent of acetaldehyd; (8) No. 3 after the addition of 0.10 per cent of acetaldehyd; (9) No. 8 after the addition of 3 per cent of absolute alcohol. After standing 30 minutes, Nos. 6, 7, and 8 possessed a brown color, and No. 9 had assumed a yellow color. At the end, of 24 hours the following results were observed : (1) Nil; (2) clear, uncolored, separate; potassium hydroxid and ether color- less; (3) very small amount of a brownish substance; (4) brown solution; no colored substance on the potassium hydroxid as in No. 3; (5) clear, uncolored, separate; no brownish substance; (6) yellow solution and considerable "aldehyd resin"; (7) as in No. 6; (8) much more considerable in amount than in No. 6; (9) red-brown solution. From these experiments it was concluded that the yellow or brownish separate is only caused by the presence of acetaldehyd, and, in cases where the ether is tinted yellow or brown, this is often due to the presence of alcohol, as well as aldehyd, the former dissolving the resin formed by the latter. Peroxids may produce a turbidity, but no coloration or colored separate. There is a source of error in the potassium hydroxid test, however. Just as spirits stored in casks made of wood containing tannin show a coloration with potassium hydroxid, so do samples of ether containing pieces of cork, the latter being introduced from the stoppers. The coloration in this case is probably due to the presence of quercitannic acid and resinous matter extracted from the cork through contact with ether. An ether containing mere traces of acetaldehyd — that is, aldehyd not detectable by the potassium hydroxid test — may thus be- come colored when the test is applied, providing it has remained in contact with cork or contains pieces of broken cork, the latter being by no means unusual owing to the form of the neck of the tin containers in use. 868 ANESTHESIA -[-15° C, but this absorbs water on exposure to the atmosphere and rises to 0.7.20-0.721 specific gravity, when it becomes fairly constant. Explanation of Changes Liable to Occur in Ether Improperly Stored. — Baskerville^ has conducted an extensive investigation on the changes which occur in ethyl ether during storage, and the experimental data obtained lead to the conclusion that the oxidation of ether in the presence of moisture is productive of a series of complex conversions, initiated, however, by the formation of hydrogen dioxid. The slow com- bustion of pure ether in the presence of water, and under such condi- tions as exist when it is improperly stored, as, for example, varying tem- perature and in sunlight, in colorless glass vessels, or in badly stoppered tin containers, would appear to occur in the following stages : (1) The formation of hydrogen dioxid from water and oxygen of the air. This is particularly likely in cases where there is direct expos- ure to light, and it is more or less activated by contact action. (2) Dissociation of hydrogen dioxid into water and oxygen, which latter then exerts a direct oxidizing action, resulting in the formation of the following: acetic peroxid, acetaldehyd, and acetaldehyd peroxid, and eventually acetic acid. The formation of acetic peroxid facilitates a series of oxidations, and, by its hydrolysis alone, acetic and peracetic acids are formed. The peracetic acid then becomes converted into acetic acid and hydrogen dioxid. Therefore, it is reasonable to conclude that a continuous cycle of changes occurs in ether during its oxidation and that such changes result in the simultaneous formation and occurrence of peroxidized compounds, intermediate (aldehyd) and ultimate (acetic acid) resultants. The Purification of Ether Remnants with the View of Removing Aldehyd in Particular. — Several methods have been devised for the re- moval of aldehyd from ether. Some are secret. Although it is exceed- ingly difficult to eliminate this impurity completely, yet it has been done commercially and the anesthetist should insist upon his ethers being free from aldehyd. Treatment with potassium hydroxid or metallic sodium serves to remove not only water, but also aldehyd, and an ether so treated con- tains mere traces of the latter impurity. Lassar-Cohn - has found that ether may be most satisfactorily freed from alcohol and aldehyd, how- ever, by boiling it with a reflux condenser for twenty-four hours with an alloy of potassium and sodium. The application of any method should not be undertaken by any except an experienced chemist. Acidity of Ether and Effect Thereon of the Container. — It has been ^ Assisted by Hamor, J. Ind. Eng. CJiem., 3, Nos. 5 and 6. ^ Ann. 284, 226. This alloy is fluid at low temperatures, and is superior to metallic sodium in that it is not liable to become encrusted with a protective layer of hydroxid and resin. APPENDIX I 869 only within the last twenty-five years that serious attention has been given to the detection of acidity in the various anesthetic ethers. None that we have examined contained acids (sulphurous, sulphuric, acetic) in what may be termed injurious amounts, since the amount present never exceeded 0.003 gm. of acetic acid per 100 c. c. of the sam- ple in any instance. The degree of acidity is liable to vary more or less in both directions in short intervals during storage in glass vessels, just as in the case of the oxidation of ether itself. The variations in acidity — theoretical, but not in general sensible — may be due to differences be- tween the rapidity of the oxidation and the saturation of the acids by the bases of the glass. In fact, the nature of the ether container is of vast importance in the light of the oxidation changes which are possible. The extent of the oxidation — or, for that matter, any oxidation at all — is dependent upon the quality of the glass used in bottles for storing ether; and in the case of metallic containers, in view of some recent re- searches, it is probable that all metals which show anomalous anodic conductivity are likely to develop free hydrogen dioxid in contact with water and oxygen. The presence of such metals should, therefore, be guarded against. Physiological Consideration in Reference to Small Amounts of Impurities. — The presence of small amounts of substances has often- times been the cause of a chemical reaction proceeding in a particular direction by virtue of a so-called "catalytic" or other kind of action. So the presence of even traces of certain substances, as peroxidized com- pounds, aldehyd, etc., may have caused some reactions to be incorrectly explained, or to follow an unusual, or unaccounted for, route. This is certainly true of the animal body, wherein the courses of the myriad chemical reactions coincident with life processes, if they be not really such, are affected by the presence of the anesthetic and undoubtedly made to take queer directions by the simultaneous presence, even in small amounts, of an unsuspected constituent. The Degrees of Purity of American Ethyl Ethers Used for Anes- thesia. — The main impurities contained in American ethers are, beside alcohol and water, acetaldehyd and acids. As previously noted, the presence of small amounts of alcohol is permissible or may even appear necessary; but anesthetic ethers should contain but mere traces of moisture, and, as has been indicated, it is desirable that they should be absolutely water-free. This would undoubtedly increase the cost of pro- duction; however, so long as ether is supplied in small tins of such a size that the contents are used completely at an operation or that, not used, being little, may be discarded, and not stored, it is only neces- sary that the amount of moisture present be reduced to very low per- centage. The following table will serve to show the comparative purity of 870 ANESTHESIA three samples of anesthetic ether, purchased in the open market by Gwathmey and submitted to Baskerville, numbered, and without the latter knowina: the name of the manufacturer : Test D E F Sp. gr. at 25° 0.7162 No foreign odor 98.50% 0.5% None 0.0006 Negative None Present* Present in permissible amount 5.00% None Present in permissible amount 0.7189 Id. 97.00% 2.00% Id. 0.00015 Id. Id. Id. Excessive 6.00% Id. Id. 0.7161 Odor Ether distillate Id. 97 . 50% Distillate above 36° 1.50% "Organic impurities" Id. Relative acidity in gm. acetic acid in 100 c.c 0.00165 U. S. p. litmus test Id. Residue Id. Water Id. Alcohol As in No. D Relative total impurity (Allen's ap- proximate method) 5.50% Peroxids Id. Aldehyd Excessive as compared to others ^ In all three samples the amount of water present was not excessive providing the ether would be properly stored or at once consumed completely by the user. All the samples were properly canned. The samples of "D" examined possessed a relatively higher degree of uniformity than the samples " E " and " F. " The American product is universally recognized as of high grade; however, not suflScient attention has been given to the storage of ether by the user, and until the latter cooperates with the manufacturer, fully and intelligently, the results obtained may continue to be variable, and rigid requirements on the part of the producer are useless. How- ever, the purer the product to begin with the better results are to be expected. Ether freed from moisture and all but traces of aldehyd by means of sodium or other methods is not required in this country for anesthetic purposes, and it is generally considered satisfactory if no "after-effects" are observed. APPENDIX II 1 CHLOEOFOEM History of Chloeoform. Preparation of Chloroform : From Ethyl Alcohol ; From "Methy- lated Spirit"; From Acetone; From Methane; From Carbon Tetra- chlorid. Varieties of Chloroform of European Make: Chloral Chloro- form; Chloroform Pictet; Chloroform Anschiitz. Purification of Chloroform. The Decomposition of Chloroform: The Changes Which Chlo- roform Undergoes Upon Exposure to Air. Verified Tests for Purity of Anesthetic Chloroform : Odor ; Eesidue ; Specific Gravity ; Organic Impurities ; Acetone ; Acetaldehyd ; Acidity; The Decomposition Products of Anesthetic Chloroform. Degrees of Purity of American Chloroforms. History of Chloroform. — Silliman ^ confused chloroform with ethy- len dichlorid, stating that it had been "long known to chemists under the name of '^oil of the Dutch chemists' and 'Dutch oil/ from its discov- ery in 1796 by an association of Dutch chemists." In 1831 Liebig '^ obtained chloroform by the action of a water solu- tion of potassium hydroxid on chloral and by treating acetone with bleaching powder. Almost at the same time, however, Soubeiran ^ ob- tained chloroform by the action of bleaching powder on dilute alcohol, terming the product "ether bichlorid," and he was regarded as the dis- coverer of the compound until Liebig ^ advanced his claim as having been the first to prepare it, although he originally believed the substance to be a new chlorid of carbon. According to some writers,^ Samuel Guthrie discovered chloroform ^ Much of this appendix is taken from a paper bj Baskerville and Hamor : /. Ind. Eng. Chem., 1912, 4, Nos. 3, 4, 5, 6, 7. 2 Am. J. Sci., 5, No. 2, 240. ^Pogg. Ann., 23, 444; Ann., 1, 31, 198. * Ann. chim. phys., 48, No. 2, 131; Ann., 1, 272; Soubeiran and Mialhe: Ann., 71, 225. 5 Ann., 162, 161. ^E. g., Wurtz. 871 872 ANESTHESIA simultaneously with Liebig and Soubeiran, and it has also been stated ^ that his discovery antedates that of Liebig by several months. Silliman ^ stated in 1848 that "the production of 'chloric ether,' so-called, by the action of alcohol with bleaching powders, was discovered almost simul- taneously and without conference by ovir ingenious countryman, Samuel Guthrie, of Sackett's Harbor, New York, and by M. E. Soubeiran in France." Liebig considered that he had prepared carbon trichlorid, whereas he actually obtained chloroform, and Guthrie confused his own product with ethylene chlorid; in both cases the investigations were made in 1831 and published in the early part of 1832. Guthrie prepared chlo- roform without knowledge of the work of Liebig or Soubeiran, and is fully entitled to be credited with its independent discovery.^ Dumas,* in 1834, showed that chloroform contains hydrogen, and later he determined its true formula.'^ Dumas obtained chloroform by boiling tri-chloro-acetic acid with aqueous alkaline solutions, and it was iPop. Sci. Moil., 12, 738. 2 Log. cit. 3 The attention of Guthrie appears to have been directed to the preparation of "chloric ether" by reading a passage in a work by Silliman ("Elements of Chem- istry," 2, 20), wherein it was stated that the alcoholic solution of "chloric ether" is of medicinal value. By the term ' ' chloric ether ' ' Silliman referred unmistak- ably to ethylene chlorid, which Guthrie considered he had prepared in ' ' spirituous solution" by the action of chlorid of lime on alcohol of density 0.844, whereas he actually obtained an alcoholic solution of chloroform (Am. J. Sci., 21, No. 2, 64). Silliman, commenting on Guthrie's original contribution {ibid., 408), stated that "we cannot say precisely what takes place during the distillation of alcohol from chlorid of lime. It is, however, worthy of notice, that, as alcohol is be- lieved to be composed of olefiant gas and water, . . . and as chloric ether has been heretofore produced by the combination of chlorin and olefiant gas, it seems hardly to admit of a doubt, that in distilling alcohol from chlorid of lime, the latter gives its chlorin to the olefiant gas of a part of the former, and thus produces chloric ether, which passes over, in solution, in another portion of the alcohol, while the water of that portion of the alcohol which afforded the olefiant gas, or the water which may be supposed to be produced by a combination of the elements, is detained by the lime. ' ' The question was raised, ' ' Can any method be devised by which the alcohol can be detached from the chloric ether, and the latter obtained concentrated and in quantity?" Guthrie later {ibid., 22, 105; see also, Hayes: Ibid., 163) found that this could be accomplished by distillation over sulphuric acid, and obtained an "ether" possessing a density of 1.486 and boiling at 166° F. In a communication to Silliman, he stated that "as chloric ether is said to have a specific gravity of only 1.22, at 45° F., a boiling point at 152° F., and to be decomposed by sulphuric acid, evolving chlorin, you may have good reason to doubt the purity of my product, or the accuracy of my estimate, but you can very readily verify the first, and I shall be found to be very near the truth with the latter. ' ' iAnn. chim. phys., 56, No. 2, 115; Ann., 32, 113. 6 Ann. chim. phys., 71, No. 2, 353. APPENDIX II 873 he who gave the compound its present name.'^ Eegnault ^ proved that chloroform is the second substitution product of methyl chlorid; he termed it "ether hydrochlorique de methylene bichlorure." Bcrzelius referred to chloroform as "formylsuperchlorid," and Mitscherlich as "chloratherid." Preparation of Chloroform. — From Ethyl Alcohol. — Soubeiran showed that chloroform is made by the action of "bleaching powder" on dilute ethyl alcohol.^ When ethyl alcohol of various strengths is poured upon "bleaching powder" and distilled, the distillate affords an oil which may be separated by fractionation.* A small amount of ethyl chlorid is also formed.'' According to the process of Schering/ chloroform is produced when halogen salts of the alkalies or alkaline earths are electrolyzed in the presence of alcohol, acetone, or aldehyd in a warm aqueous solution. '^ Although ethyl alcohol was formerly used for the production of chlo- roform, it is now largely, or almost entirely, replaced by acetone. Kecently carbon tetrachlorid has become an important source of chloroform. From "Methylated Spirit." — Pure methyl alcohol does not yield chloroform when treated with bleaching powder, although it is formed from commercial methyl alcohol.^ "Methylated chloroform," at one time extensively used in England, is chloroform prepared from wood ^ Ibi(T., 56, No. 2, 120. To quote Dumas: "La formule . . . correspond a une chlorure d'hydrogene carbone, qui est 1 'equivalent de I'acide formique an- hydre . . . C'est ce qui m 'engage a la designer sous le nom de chlorof orme. " ^Ihid., 71, No. 2, ^17 ; Ann., 33, 328; J. pralct. Chem., 19, 210. ' See also, Bechamp : Ann. cJiim. phys., 22, No. 5, 347. For papers on the manufacture of chloroform from alcohol and ' ' chlorinated lime," see Am. J. Pharm., 1862, 25, 42; 1868, 289. In Chem. Ztg., 10, 338, is described the process in use in Germany in 1886; see also Frerichs: Am. Inst. Chem. Eng., 1911; J. Ind. Eng. Chem., 4, No. 5. On the preparation of chloroform from alcohol, see, in addition, Goldberg: /. pralct. Chem., 132, 111; Soubeiran: Compt. rend., 25, 799; Meurer: Chem. Centr., 1848, 154; Carl: Ibid., 1848, 236; Larocque and Hurault: N. J. Pharm., 13, 97; Siemerling: N. Br. Arch., 53, 23; Kessler: N. J. Pharm., 13, 162; Eam- dohr: N. Br. Arch., 83, 280; and Hirsch: IMd., 107, 137. The alcohol used should not contain fusel oil [Regnault and Hardy: J. pharm. chim., (4), 30, 405] or higher alcohols. *Dott (/. Soc. Chem. Ind., 27, 6, 271) gives the reaction: SC^HsOH + 8Ca(OCl)2 = 2CHCI3 -f 3CaC03 + CO^ + 8H,0 -f SCaCl^. ° Finnemore and Wade: J. Chem. Soc., 85, 938. 'German Patent 29771, 1884; Ber. 17, 624; also Dony-Hennault : Z. EleJc- trochem., 7, 57. 'Kempf {Eng. Pat. 8148, 1884) invented a process for the manufacture of chloroform by electrolyzing suitable halogen compounds of the alkalies and alka- line earths in alcoholic solution with constant heating; and Trechinski (J. 'Buss. Phys.-Chem. Soc, 38, 734; Pharm. Ztg., 51, 523) prepared chloroform by the electrolysis of an aqueous alcoholic solution of calcium chlorid. ^Belohoubek: Ann., 165, 349. 874 ANESTHESIA spirit ("methylated spirit").^ It is incorrect to suppose that "methy- lated chloroform" has received an actual addition of methyl alcohol, but such chloroform is liable to be much less pure than that obtained solely from ethyl alcohol. According to Allen,^ chloroform prepared from "methylated spirit" is more difficult to purify than that made from ethyl alcohol alone; but a product has been manufactured in England from the former source which appears to be equal in all respects to that prepared from straight ethyl alcohol.^ From Acetone. — The preparation of chloroform from acetone was referred to by Liebig in 1832. Bottger, in 1848, showed how to pre- pare chloroform from acetates and from acetone. The process was not quickly followed probably, as indicated by Squibb,* on account of the erroneous statements of Siemerling (1848) and Wackenroder, adopted by such authorities as Gmelin and Watts. ^ Orndorff and Jessel ** found that the products formed by the action of bleaching powder on acetone are chloroform, calcium hydroxid, calcium chlorid, and calcium acetate. Numerous patents '^ have been granted. Chloroform is now made by electrolysis of sodium (or other) chlo- rid in acetone.® A strong prejudice in the pharmaceutical trade against ^ ' ' Methylated spirit " is a mixture of rectified spirit with 10 per cent of wood alcohol (methyl alcohol) ; it has been used in the manufacture of chloroform owing to its being obtained duty free (Thorpe). ^"Commercial Organic Analysis," 3908, 1, 235. "Methylated chloroform" is not on the American market. ^ Allen is also authority for the statement that imperfectly purified ' ' methy- lated chloroform ' ' is specifically lighter than the pure substance, 'has an em- pyreumatic odor, and produces disagreeable sensations when inhaled. In some cases, we are told, such chloroform appears to be actually poisonous, and pro- duces general and rapid prostration. Such chloroform contains several units per cent of a chlorinated oil, lighter than water and boiling at a much higher tem- perature than chloroform. A similar but different oil (heavier than water) has been detected in much smaller quantity in chloroform prepared from alcohol con- taining no methyl compounds; these oils may be totally eliminated by purification of the crude chloroform. V. Am. Chem. Soc, 1896, 231. ^A Dictionary of Chemistry, 1, 918; also Siemerling: Arch. Pharm., S3, No. 2, 23. ^ Am. Chem. J., 10, 366. Dott (Pharm. J., 81, 54) found that there are also considerable amounts of calcium carbonate and chlorate in the residual liquor ob- tained in preparing chloroform from acetone. "Michaelis, U. S., 322,194 (1885); Michaelis and Meyer, England, 8523, (1880) and Germany 36,514 (1886) ; Eumpf, U. S., 383,992 (1888) ; Porsch, U. S., 573,482 (1896); Chute, U. S., 893,784 (1908). "■Bev. Prod. CMm., 3, 309; Klar. Chem. Ind., 19, 159. Teeple (J. Am. Chem. Soc, 26, 536) found that the conditions necessary for the successful preparation of chloroform by the electrolysis of a chlorid in the presence of acetone are: A temperature below -(-25° C, absence of alkali, a high current density at the cathode and a low one at the anode. APPENDIX II 875 chloroform from this source doubtless had somethiu"^ to do with causing manufacturers to be reluctant about divulging any information concern- ing the process. Feom Methane (ISTatural Gas). — Pennsylvania natural gas con- tains 50-95 per cent of methane/ and, bearing i]i mind tjie dcmionstra- tion of Regnault - that chloroform is formed by the action of cihlorin on methane in daylight and quickly in sunlight, several investigators have sought to effect a chlorination in order to obtain substitution products. So far, although numerous patents have been secured, no process for making chloroform from methane has been operated com- mercially with success.^ From Caebon Tetrachlorid. — Geuther found that chloro- form results from the action of nascent hydrogen (from zinc and sulphuric acid) upon carbon tetrachlorid.* It was not until successful commercial processes for the production of carbon tetra- chlorid had been developed, however,^ that it was ascertained that chloroform might be advantageously prepared from carbon tetra- chlorid. In 1902 A. W. Smith devised a process of making chloroform from carbon tetrachlorid, which process consists of the following stej)s : The action of heated sulphur upon heated carbon, so as to produce carbon disulphid ; the action of chlorin upon sulphur, so as to produce sulphur chlorid or dichlorid; the action of sulphur chlorid or dichlorid upon carbon disulphid, so as to produce carbon tetrachlorid; and, finally, the reduction of carbon tetrachlorid, so as to produce chloroform. It has been stated that "technically piire" chloroform produced from disul- phid-tetrachlorid may be recognized by its small content of carbon di- sulphid and carbon tetrachlorid, and that such a grade also possesses a higher refractive index than other varieties. "Anesthetic chloroform" made from carbon tetrachlorid conforms in full with the required pharmacopeial standards. From chemical evidences, any prejudice at- ^ Pennsylvania natural gas contains from 50 to 99 per cent total paraffins ; Ohio gas, 90 to 93 per cent; and West Virginia Jas, 80 to 87 per cent. ^ Ann. chim. -phys., 71, No. 2, 380. ^ These processes are summarized in the paper by Baskerville and Hamor, loc. cit. "■Ann., 107, 212. ° As early as 1834 it was learned that carbon disulphid may be converted into carbon tetrachlorid by chlorination (Kolbe: Ann. 45, 41; 54, 146; see, also, Hofmann: md., 115, 264; Klasow: Ber., 20, 2376; Mouneyrat: Bull. soc. chim., 19, No. 3, 262; and Serra: Gaz. chim. ital, 29, 353). Muller and Dubois {'Eng. Fatent 19,628, 1893) devised a process for the production of carbon tetrachlorid by the addition of a finely divided iron to a mixture of carbon disulphid and sulphur chlorid; cf. Eng. Patent 13,733 of 1901, of Urbain, wherein practically the same process is claimed; and V. S. Patent 753,325, dated March 1, 1904, cf A. W. Smith. 876 ANESTHESIA tached to such chloroform is without foundation, and there should be no hesitancy in disclosing the source. Varieties of Chloroform of European Make. — Considerable quanti- ties of chloroform are produced in Germany by special purification processes for domestic and foreign consumption.^ Some of these are on the American market. In addition to anesthetic chloroform prepared by the action of bleaching powder on alcohol and acetone (Chloroform Gehe, Riedel, Merck, Kahlhaum, de Haen, Konig and Cotta), "chloroform e chlo- ral/' "chloroform Pictet/' and "chloroform Anschiitz" are found on the German market. Chloeal-Chloeofoem. — Liebig found that chloroform may be pre- pared by distilling chloral with excess of aqueous potassium hydroxid, sodium hydroxid, or baryta, or with milk of lime, repeatedly agitating the oily distillate with water, separating from the water as completely as possible by decantation, and then distilling with 6 or 8 times its vol- ume of strong sulphuric acid in a perfectly dry apparatus. In 1870 chloral-chloroform was sold under the name "English Chloroform" in Germany, and Hager, after an examination, expressed the opinion that chloroform from chloral was the purest then obtainable.^ The invention of Liebreich ^ for preparations for the production of chloroform relates broadly to a product consisting of a dry mixture of chloral hydrate and alkali, which may be compressed into any con- venient shape; on treatment with water chloroform is produced. The product of this process has been known as "chloroform Liebreich," and "chloroform Sobering," now on the American market, is prepared from Liebreich's crystallized chloral hydrate. Langgaard * examined the eight principal brands of chloroform ob- tainable in Germany, and found that chloral-chloroform was the purest. ^In 1910, for example, 161,900 kg. of chloroform and chloral were exported, 19,000 kg. of which went to the United States; the average price was from 170 to 180 marks per 100 kg. 'Year-Boole of Pharm., 1870, 119. Hager found that "English chloroform" was really chloral-chloroform containing 0.75 to 0.80 per cent of alcohol. The addition of pure sulphuric acid to this chloral-chloroform caused no coloration, while it was found to color slightly the ordinary grade of chloroform then in use. Evaporation of some of the substance on a watch-glass in the air was found to afford another means of testing the substance. When all but a few drops had disappeared, the ordinary chloroform residue was found to possess a disagreeable odor, while the other retained its pleasant odor. Versmann (Pharm. J., 2, No. 3, 63) also found that the residue of chloral chloroform possessed no foreign odor.. According to a later writer, however (Arends: Pharm. Ztg., 1891, 263), Ger- man chloroform is generally superior to that manufactured in England. The British Pharmacopoeia is considerably less stringent than that of Germany. ^Eng. Patent 15,930, 1904. *Therap. Monatsch., May, 1902. APPENDIX II 877 As a general rule, however, all of the German chloroforms of anesthetic grade are of good quality/ and the grade at present pres(;ribed by the Arzneihuch is, at least in most cases, equal to chloroform prepared from chloral. It has also been claimed that chloral chloroform does not undergo decomposition, but this has been shown to be incorrect; ^ in fact, like all the other pure preparations, "chloroform e chloral" decomposes if not preserved by the addition of a little alcohol.^ Chloroform Pictet. — This preparation is obtained by crystalliza- tion at a low temperature, followed by fractional distillation (referred to again later). Schacht has shown that, although the Pictet chloro- form is a good preparation, that obtained from the purest crystallized chloral hydrate is quite equal to it, and, like the latter, it requires a preservative to keep. Chloroform AnschiItz. — More recently a special preparation un- der the name "Anschiitz salicylid chloroform" or "Salicylchloroform" has been placed on the German market; it is obtained from a crystalline compound of salicylid, and was first prepared by Anschiitz.* Purification of Chloroform. — The crude chloroform prepared by the action of bleaching powder on alcohol; by the action of bleaching powder on acetone f or by the electrolysis of solutions of chlorids of the alkalies or alkaline earths in alcohol or acetone,*' is not of so high a de- gree of purity as that obtained by the action of alkalies on previously purified chloral, and requires more careful purification before it is suit- able for anesthetic purposes. The extent of the purification necessary is dependent upon the purity of the materials used as well as upon the process employed. ^ The results obtained by Baskerville and Hamor in the course of an examina- tion of the principal German products may be found in their paper, loc. cit. 'See Am. J. Pharm., 42, 409. = See Schacht: J. Soc. Chem. Ind., 1893, 543. *J. Soc. Chem. Ind., 1893, 782. According to the patented process of An- schiitz, chemically pure chloroform is produced by decomposing by heat double compounds of chloroform and lactid-like condensation products, derived from orthophenol carbonic acids, as salicylid, and then condensing the pure chloro- form; salicylid-chloroform is prepared by boiling salicylid in chloroform (U. S. Patent 535,270, 1895), and in this compound chloroform plays the same role as the water of crystallization in many crystalline salts, being obtained in a pure state by simple distillation therefrom (Anschiitz: Ann., 273, 94; Arends: Chem. Ind., 16, 78). Salicylid-chloroform is said to be extensively used by anesthetists in Eussia, it conforming to the pharmacopoeia of that country, and is especially recommended for anesthesia by many. The comparative prices of chloroform prepared from acetone by means of bleaching powder, chloroform from chloral by potassium hydroxid, "chloroform Pictet, ' ' and ' ' chloroform Anschiitz, ' ' are, respectively, taking the first as a basis, 1^ 3, 6, and 9. "See Pharm. J., M, No. 3, 84. »jSee J. Soc. Chem. Ind., 1885, 243. 878 ANESTHESIA The earliest methods for the purification of crude chloroform con- sisted in washing the distillate with water to remove alcohol/ and then drying over calcium chlorid, or sometimes rectifying without having previously dried the product. In 1848 the crude chloroform was puri- fied by shaking with potassium hydroxid, drying over calcium chlorid, and then rectifying ; this method served to remove chlorin ^ and acids, but it only partially eliminated alcohol and other probable contam- inants. Gregory^ purified chloroform by agitating it and leaving it in con- tact with sulphuric acid until the latter was no longer colored by it; then he removed the chloroform and placed it in contact with a small quantity of manganese dioxid to free it from "sulphurous acid." About 1860 the German custom was to rectify overconcentrated sulphuric acid.* At the present time treatment with sulphuric acid is generally resorted to, and forms the most important stage of the purification of crude chloroform prepared from alcohol or acetone. Pure concentrated sulphuric acid has no action on chloroform itself unless the operation is unduly prolonged,^ but it decomposes some of the impurities which are commonly present, and removes others. In the next place, the ^ When made from alcohol, crude chloroform contains considerable quantities of alcohol in solution, from which it may be separated by repeatedly washing with water. In order to wash a yield of 160 to 175 kg. of crude chloroform, about 800 liters of water are necessary to obtain anesthetic chloroform, although this washing forms only one stage of the purifying process. ^ Kessler [J. Pharm. Chim., 13, (3), 162] found that chloroform may be freed from chlorin by agitation with potassium hydroxid, and suggested that it be further purified by drying over calcium chlorid and followed by rectification. ^ Proc. Eoy. Soc. Ednh., 1850, 391. According to Abraham {Pharm. J., 10, 24) chloroform, when thus purified, quickly decomposes, and is afterwards found to contain hydrochloric acid and free chlorin. * The United States Pharmacopoeia of 1850 gave a process for preparing chloroform; this was transferred in 1860 to the Materia Medica Catalogue. ' ' Chloroform venale, ' ' or commercial chloroform, was introduced and also a formula for purifying chloroform; this was dropped in the Pharmacopoeia of 1890. ° Christison {Pharm. J., 10, 253) found that chloroform keeps well after being once treated with sulphuric acid; but that the continued action of that liquid, especially if it is contaminated with nitrous acid, exerts a decomposing action on it. Tilden {ibid., 1, No. 3, 623) stated that the sulphuric acid used to purify chloroform must be free from all traces of nitrogen oxids; and it was his opinion that the decomposition of chloroform may be attributed to contamination of this kind. Eedwood {ibid., 12, No. 3, 734) was inclined to ascribe the improved quality of the British chloroform of 1882 to the care used in its manufacture, particularly to the attention paid to the purity of the sulphuric acid used in the purification. Clark, however, maintained that the presence cf nitrous or nitric acid in the sulphuric acid was not the cause of the instability of chloroform. Both Clark and Dott considered ' ' that the decomposition of chloroform is not probably due to the presence of nitric acid in the sulphuric acid" {vide Preston, ibid., 12, No. 3, 981). APPENDIX II 879 product is brought in contact with sodium carbonate/ or it is washed with lime water and then dried over calcium chlorid.^ In any case, it should be finally distilled at a temperature not above -(- 64° C.^ Various other methods have been proposed for the purification of chloroform, especially when it has become contaminated with decom- position products. We have, for example, the method of Gibbs, wherein lead dioxid is employed ; * that of Mentin, according to which the chlo- roform is distilled over 2 per cent of paraffin at 61°;^ and the recom- mendation of Shuttleworth "^ that agitation with a dilute solution of sodium thiosulphate be employed^ * Shuttleworth (Am. Chemist, 4, 339) observed that in samples of chloroform imperfectly rectified, as that of the ordinary German manufacture of 1873, the impurities produced by the agencies of time, light, moisture, and atmospheric ex- posure are, after a lapse of some months, easily recognizable. Traces of sulphuric acid were found to quickly induce this change; and when that chemical has been employed as the purifying agent, and has not been completely removed by re- peated washings and rectifications, the product will very soon give sharp indica- tions of decomposition. The method of purification adopted by the British Phar- macopoeia of that time consisted in mixing the chloroform after treatment with acid, with lime and calcium chlorid, and then rectifying at once. Shuttleworth considered that the keeping qualities of the product would be much improved by agitating the chloroform, followed by washing with water. Werner (Arch. Pharm., 25, No. 3, 1113) stated that his method of purification afforded a product found to be perfectly satisfactory for medicinal use during 10 years' experience. This method (ibid., 1^, No. 3, 481) consisted in shaking the chloroform with one- fourth its volume of distilled water, removing the latter the next day, then agitat- ing the chloroform with fused sodium carbonate, and allowing the mixture to stand for 24 hours. After removing the sodium carbonate the residual product was dis- tilled on a water bath, the distillate coming over below -f- 64° C. being used. ^Thayer (/. Physical Chem. 3, 36) found that traces of alcohol remained in chloroform even after the latter had been allowed to stand over calcium chlorid for a long time. He purified chloroform by washing it repeatedly with water, then keeping it in contact with calcium chlorid for two days, and finally decant- ing and distilling over fresh calcivim chlorid. *See Werner, loc. cit.; Thorpe, loc. c%t.; Eemys, Archiv Pharm., 5, III, 31; and Michaelis and Mayer, Polyt. J., 261, 49G. * Trans. N. Y. Acad. Med., 1, 146. Gibbs suggested, in 1850, that chloroform possessing an acid reaction and probably containing chlorinated oils be treated with lead dioxid. Metcalfe (ibid.) found that such treatment served to remove any disagreeable odor characteristic of such chloroform. ^ Ann. chim. fran., 10, No. 4, 32. '^ Am. Chemist, 4, 339. Shuttleworth recommended that chloroform which has been injured by time exposure be restored by agitating well with a dilute solution of sodium thiosulphate, separating from the supernatant liquid and washing with water, then separating and passing the chloroform through filter paper to free it from traces of moisture. " Although this method yielded an improved chloroform, Shuttleworth consid- ered that, when a pure preparation is desired, the impurities not removable by thio- sulphate, those of a more stable character and possessing a higher boiling point than chloroform, be removed by distillation or by treatment with sulphuric acid. 880 ANESTHESIA Yvon ^ stated that he was enabled to obtain an absolutely pure chlo- roform by treatment with an alkaline potassium permanganate solution ; this procedure has not come into use. Useless also, providing the chlo- roform has been brought to the proper state of purity prior to frac- tionation, is the French practice of distilling over poppy oil.^ In the process of Pictet ^ commercial chloroform is cooled to — 80° C, and the solid bodies are removed by filtration; it is then cooled to — 82° C, and the non-crystallizable portions, which contain impurities, are removed ; the solid chloroform is melted and then distilled at a very low temperature, under reduced pressure, and the middle 80 per cent of the product is taken as "chemically pure" chloroform. On its introduction it was announced that "chloroform Pictet" had been experimentally proved to possess a capability of resisting the influ- ence of sunlight for four days. Schacht and Biltz * therefore inferred that it contained alcohol, and their prediction that such was the case, without even having seen a sample, ultimately proved to be the case. Moreover, Schacht ^ found that "chloroform Pictet" suffers the usual de- ^ Mon. Sci., Mar., 1882, 262. Yvon found that chloroform prepared according to the French Pharmacopoeia of 1866, by agitating with water, leaving in contact with potassium carbonate, drying over calcium chlorid, and finally rectifying, is sufficiently pure for anesthetic purposes. He pointed out, however, that a still purer product could be obtained by modifications of this method. ^ The method official in the French Pharmacopoeia of 1899 for the purification of commercial chloroform was modified by Masson (J. pharm. chim., 9, 568), ac- cording to whose process crude commercial chloroform is first washed with water, the aqueous layer separated, and the chloroform shaken with 2.5 per cent of its weight of sulphuric acid, and the operation being repeated with a fresh portion of acid, if necessary, the acid being left in contact with the chloroform for two or three days. The chloroform is then treated with 3 per cent of its weight of sodium hydroxid solution (sp. gr., 1.33) which is left in contact also for two or three days. It is then washed with water, dried over calcium chlorid, and 2.5 per cent of poppy oil added. Distillation is then conducted into graduated re- ceivers containing 0.2 per cent by weight of alcohol for the amount of chloroform they are to contain. The important modifications of this process are: the pro- longed contact of the chloroform with the sodium hydroxid solution; the final distillation over poppy oil (it was then employed in the official process for a pre- liminary distillation) ; and the presence of a trace of alcohol in the receiver. The "Chloroforme Officinal" of the present Codex (1908, 148) is prepared from rectified commercial chloroform by agitating with distilled water, decant- ing and filtering; shaking with sulphuric acid, then allowing to stand over sodium hydroxid; drying over calcium chlorid, and finally distilling over poppy oil and adding alcohol (5/1000 part by weight of absolute ethyl alcohol). See also, Maillard and Eanc: Compt. rend. Soc. biol., 61, 483. ' U. S. Patent 489,592, 1893; and English Patent 15,514, 1891; see also J. Soc. Chem. Ind., 18, 231. On some peculiar phenomena in the solidification of chloro- form, see Pictet: Compt. rend., 114, 1245. *J. Soc. Chem. Ind., 12, 543; see also. Western Drug., 1891, 379. ^ Pharm. J., 22, No. 3, 691. APPENDIX II 881 composition, on washing to remove alcohol ; and Biltz ^ regarded the decomposition of chloroform under the influence of light and air as a natural characteristic of chloroform, and not as a result of impurities." However, DuBois-Reymond ^ stated that "chloroform Pictet" is affected less by sunlight than any other chloroform with even the addition of alcohol.* J. F. Macfarlane & Co.^ separated the following relative quantities of "impurity" from "chloroform Pictet" and a British product. From domestic product 0000512 per cent. 0.0002050 " " "chloroform Pictet" . 0008200 " " " " 0.0004100 " The "chloroform Pictet" examined by Baskerville possessed a density of 1.491 at 15/15° C, and all the tests for the presence of impurities and decomposition products gave negative results. Four other German products and one American anesthetic chloroform, all of which were purified by chemical treatment, were found to be fully as pure, however, which indicates that purification by cryogenic means is not necessary to secure chloroform of anesthetic grade. DuBois-Eeymond '^ has studied the physiological action of "chloro- form Pictet" and of the residue of foreign substances obtained in the process of Pictet. He found that the shape of the pulse waves and the frequency of respiration are about equally affected by both substances, the rate of respiration varying freely; that the pulse rate, compared in nineteen cases, is higher at the close of the experiments with the residue than with those with the purified chloroform ; that the blood pressure in by far the greater number of experiments at the moment respiration ceases is higher after inhalation of the purified chloroform than after in- halation of the impure residue ; and, finally, that the residue causes stop- page of respiration much more quickly than does purified chloroform. DuBois-Reymond conducted hardly a sufficient number of physiological experiments to enable one to form a definite opinion of the physiologi- cal action of the commonly occurring impurities of commercial chloro- form which are separated by means of the process of Pictet. In addi- tion the variable nature of these impurities, owing to the various proc- * Ibid. 'See also, Biltz: Ber. Pharm. Ges., 2, 76, 247; Schacht: Ibid., 2, 69; and Thilo : Pharm. Ztg., 39, 543. ^ Pharm. Centralh., S2, 658. * Had DuBois-Eeymond made his comparisons of ' * chloroform Pictet ' ' with properly purified samples of anesthetic chloroform, no such differences as he re- ported would have been observed. ^Brit. Med. J., 1892, 1, 525. ^Brit. Med. J., 1892, 1, 209. 882 ANESTHESIA esses of manufacture and the variability of the crude materials used therein, renders such an investigation of little value. When acetone is used for the preparation of chloroform, it should be previously purified/ and this purification should be carefully executed in order to prevent the formation of condensation compounds.^ It has been stated that chloroform made from acetone is not nearly so good an anesthetic as chloroform made from ethyl alcohol ; ^ but this opinion is based upon the findings of Wade and Finnemore ; * that chlo- roform prepared from ethyl alcohol contains a very small proportion of ethyl chlorid. When chloroform is properly made from purified acetone careful purification will result in the production of pure chloroform.^ Gregory ® found that the chloroform prepared from ethyl alcohol and wood spirit, when fully purified, is quite identical in all its proper- ties, but that from the former is more easily purified. In fact, it may be asserted on the authority of Brown, Squibb, Schacht, and Biltz '' that properly purified chloroform is the same from whatever source it is obtained ; however. Cross and also Spilsbury ^ have expressed the opin- ion that chloroform made from ethyl alcohol is physiologically safer than that from methylated spirit and acetone. The latter opinion is a ^ In Am. J. Pharm., 1889, 321, is an account of a method for purifying ace- tone used in the preparation of chloroform. *Dott {J. Soc. Chem. Ind., 27, 272) has called attention to the importance of the impurities which may be present in commercial acetone. He found that samples which indicated 99 per cent by the iodoform test and other methods gave about 7 per cent distilling above 58°. This was first thought to be due to the presence of higher ketones or other bodies yielding iodoform, but Gibson sug- gested that it might possibly be caused by the presence of even 1 per cent of a mixture of the condensation products of acetone (e. g., mesityl oxid, phorone, and mesitylene), which all have relatively high boiling points. It was found that, on mixing pure acetone with 1 per cent of the mixed condensation products, it behaved on distillation and in its iodoform yield, and otherwise, like the samples referred to. When purifying acetone, therefore, manufacturers should avoid treatment with mineral acids or other method which is likely to cause formation of the condensation compounds. On the purity of acetone, see also Guttman: Dingier' s Polyt. J., 1894, 96; Klar: J. Soc. Chem. Ind., 1897, 722. ^■Price: Pharm. J., 23, 89. *Loc. cit. " J. F. MacFarlane & Co. (Lancet, 1905, 1, 747) have expressed the opinion that chloroform prepared from acetone is by no means generally accepted as in- ferior to chloroform prepared from alcohol, and consider that up to the present InsuflBcient evidence has been adduced to establish the view that it is actually inferior. We may state here that, from our experience, anesthetic chloroform manufac- tured from acetone has been found by American anesthetizers, to be fully as satisfactory as that from other sources. «Mon. J. Med. Sci., May, 1850; Pharm. J., 9, 580. ' Pharm. J., 24, No. 3, 811. » lUd., 29, No. 4, 660. APPENDIX II 883 recent one (1909), and is substantiated, at least in part, by other evi- dence, but is totally incorrect when the chloroform is properly purified.^ The carbon tetrachlorid used is prepared from carbon disulphid (the electric furnace product), and manufacturers in the United States state that it is so free from sulphur compounds that "no part of the distillate separated from a batch of 5,000. pounds through a long fractionating column will show any sulphur compounds by the most delicate tests known." The presence of carbon disulphid in the chloroform produced is guarded against by means of a process for removing carbon disulphid from the carbon tetrachlorid used; when traces are present the tetra- chlorid is fractionated in a high column still until the distillate will give no response with tests for the presence of carbon disulphid. The distillate is considered as commercial carbon tetrachlorid, which is usu- ally guaranteed to contain 99.7 per cent of absolute CCl^. The material remaining in the still is tested for the presence of carbon disulphid, and if found absent, then the material remaining in the still is used for the manufacture of chloroform. The Decomposition of Chloroform. — The Changes Which Chlo- roform Undergoes upon Exposure to Air. — In order to secure a clear conception of this important matter it is desirable to compare the conduct of "pure" and "anesthetic" chloroform. In 1848 Morson ^ found that "pure" chloroform undergoes decom- position in the presence of light and air, chlorin, hydrochloric acid, and probably other "chlorin compounds" being formed;^ later he observed that the decomposition is variable in extent and rapidity, and that chlo- roform, when kept under water, does not decompose.* Maisch,^ how- ever, stated that chloroform containing moisture always showed the presence of "free chlorin" much sooner than dry samples. ^ It has also been stated that headache frequently occurs among workmen while bottling chloroforta made from methylated spirit, whereas the symptoms were not observed while manipulating chloroform derived from ethyl alcohol {ibid., 18, No. 4, 515). In this connection it may be noted that in one works where chloroform has been made from carbon tetrachlorid for eight years, according to a report from the officers, there has been not one case of accidental or other an- esthesia among the workmen. ^Fharm. J., 8, 69. ^ Therefore, Morson suggested the test with litmus paper and purification by repeated agitation with distilled water. ^IMd., 279. In 1850 (see Trans. N. Y. Acad. Med., 1, 146) it had been ob- served in this country that chloroform becomes acid and contains "chlorinated oils" through decomposition. ^ Proc. Am. Pharm. Assn., 1867. Chloroform of the density 1.492, dried by means of calcium chlorid, was kept in absolutely dry bottles and in bottles slightly moist, then both kinds were exposed to diffused daylight and to direct sunlight. Maisch concluded that the entire absence of water would not be suffi- cient to preserve the chloroform unaltered. 884 ANESTHESIA Hager/ investigating the question more extensively, concluded that "pure" chloroform is not decomposed by the action of light alone; but that, when chloroform is exposed to the action of the sun's rays, it be- comes decomposed, exhibits an acid reaction to test paper, and there are found, among its products of decomposition, hydrochloric acid, "chloroxycarbonic acid," ^ formic acid/ and free chlorin. Hager first pointed out that chloroform is decomposed when air has access to it, even in the dark, although very slowly.* Eump ^ made similar observa- tions, having learned that protection from light does not prevent the de- composition of chloroform; he concluded that the smallest quantity of moisture and air will, in time, induce decomposition, and that this, once started, proceeds with increased rapidity. Under these conditions, by excluding the light, Eump found that carbonyl chlorid will result. In 1883 Eegnault ^ pointed out that carbonyl chlorid is the most dangerous impurity found in chloroform, and stated that it is produced in the presence of light by the action of air on chloroform.'^ In col- laboration with Eoux, Eegnault demonstrated the formation of carbonyl chlorid from chloroform in several different ways : By the action of the spark from an induction coil on a mixture of chloroform vapor and air; by allowing air saturated with vapor of chloroform to circulate in an effluve apparatus ; ^ and by the action of ozonized air. The last experi- ment showed that the production of carbonyl chlorid is independent of tlie thermal and electric phenomena of the other two, and, along with ^ Pharm. Z. Bussland, Sept., 1869. ''Personne found that samples of chloroform liable to decomposition always contain ' ' chlorocarbonic ether. ' ' It has also been maintained that the change is attributable to the presence of allylene bichlorid. ' Kappeler (" Anesthetica, " 173) stated that formic acid and aldehyd are products of the decomposition of chloroform. * Hager found that chloroform, even if it does not exhibit an acid reaction, may be in a state of decomposition, and that this condition may be detected by the reaction such chloroform exhibits with ammonia, Avhich then yields with it vapors of ammonium chlorid. The results of Hager 's investigations gave rise to the statement which has persisted in the literature till to-day, namely, that specimens of chloroform, orig- inally of good quality, on keeping become impregnated with hydrochloric, hypo- chlorous, and formic acids. ^Archiv. Pharm., Oct., 1874. 'J. Pharm. Chim., 5, No. 5, 504. ^ Eegnault considered the accidental presence of carbonyl chlorid common at that time. * Eegnault and Eoux found that nitrogen charged with the vapor of chloroform also decomposes the chloroform in an effluve apparatus, the products being hy- drochloric acids and a mixture of CgClo, and C^CIe. Cf. the results of Besson and Fournier (Compt. rend., 150, 1118), on the action of the silent discharge on chloro- form in the presence of hydrogen. Among the chlorinated derivatives separated were CC1«, C^CU, C^TLC\, 0,01,, and C^Cls. APPENDIX II 885 the work of Eump, established the formation of carbonyl chloric! during the oxidation of chloroform. Confirmation of this was later had from the investigations of Marty ^ and Stark.^ Just what are the other products of the decomposition of chlo- roform is a question which has received considerable, but only recently very careful, attention. Brown ^ found that, while chloroform is not decomposed by the action of sunlight in the absence of oxygen, it is so decomposed when oxygen is present, yielding as products chlorin, car- bonyl chlorid, and water: 4CHCI3 + 3O2 = 4COCI2 + 2H2O + 201^: 2COCI2 -f 2H2O = 2CO2 + 4HC1. These equations have been recognized as correct by Schacht and Biltz,* and by Adrian ; ^ but Schacht and Biltz considered it necessary to add that they apply exclusively to the decomposition of chloroform which is perfectly free from alcohol. That the decomposition of chloroform is accelerated in an atmosphere of pure oxygen, is a fact which Schacht and Biltz were disposed to ascribe to the absence of nitrogen. In regard to the ultimately recognizable results of the oxidation of chloroform in particular instances — for example, in the case of anes- thetic chloroform — there is one circumstance which exercises a decided determining influence; but, as indicated by Schacht and Biltz,^ it is not always sufficiently considered, and this fact has given rise to differences of opinion as to the nature of this decomposition and of its products. For instance, Eamsay ^ advanced the opinion that the only products of the decomposition of chloroform are carbonyl chlorid and hydrochloric acid, while Brown, Schacht and Biltz, and Adrian maintain that in addition to the formation of those products there is also an elimination of chlorin in the free state. Schacht and Biltz considered that this dif- ference of opinion was doubtless to be ascribed to want of attention to ^L'Union 'pJiarm., Nov., 1888. Marty found that "pure" chloroform did not remain unaffected more than two days in summer or 5 days in winter, when freely exposed to air. The same chloroform remained unaltered for 15 months in the dark, although in contact with air. With chloroform containing 0.1 per cent of absolute alcohol, no decomposition resulted even after an exposure of 15 months to continuous sunlight. ^ Pharm. J., 20, No. 3, 407. Chloroform exposed to diffused sunlight for five months contained hydrochloric acid, carbonyl chlorid, and an "oily hydro- carbon." According to Stark, the alarming dyspnea produced by some samples of chloroform when inhaled is probably due to the presence of carbonyl chlorid. ^Pharm. Soc. Ednh., March, 1893. ^PJiarm. J., 1893, 1005. "J. Pharm. Chim., 18, 5. ' Loc. cit. ''J. Soc. Chem. Ind., 11, 772. The same view was held by Breteau and Woog: Conipt. rend., 143, 1193. 886 ANESTHESIA the presence of alcohol in the chloroform experimented with/ and to the resulting misinterpretation of the chemical changes which occurred. They stated that they had succeeded in proving that the well-known in- fluence of alcohol in preserving chloroform from decomposition ^ was due to the alcohol taking up and chemically combining with the deleteri- ous products resulting from the decomposition, so as to render them innocuous. Later ^ they concluded that, though the direct products of the decomposition of "pure" chloroform were only chlorin * and carbonyl chlorid, in the case of chloroform containing alcohol the chlorin thus eliminated acted on the alcohol present, and so gave rise to the produc- tion of hydrochloric acid. In this way they accounted for the presence of hydrochloric acid in the first state of the decomposition of anesthetic chloroform,^ and considered that they had explained the point which had given rise to dispute, namely, that the elimination of free chlorin is a primary feature of the alteration. These views led to a controversy with the Browns,*' and the formation and presence of free chlorin as one of ^ See Preservation. * The correctness of this view, which has been generally favored, was consid- ered in Chapter VII, p. 290. =* Fliarm. J., 22, No. 3, 1041. * Popov (J. Huss. Phys.-Cheni: Soc, 7, 1061) studied the influence of light on chloroform dissolved in linseed oil, finding that the iodin number of the oil was lowered, owing to the action of the halogen upon the unsaturated compounds of the oil. This work does not, however, prove that chlorin is a product of the photolytic decomposition of chloroform. ^ Of. Laurent (Ann. chim. phys., 1837, 318) who found that chlorin acts on chloroform in the sunlight, forming hydrochloric acid and "CaClg. " The opinions of Schacht and Biltz, variously expressed, seem to embody this general view: The gradual disappearance of free chlorin when chloroform is undergoing de- composition is an indication of its further action on the chloroform, producing hydrochloric acid and altering the relative proportions of carbonyl chlorid and hydrochloric acid so as to increase the latter. "Schacht and Biltz (Pharm. J., 23, No. 3, 1005) stated that "decomposition cannot be detected in alcohol-reduced chloroform until all the added alcohol has been consumed." Brown (ibid., 24, 321) found that "pure" chloroform to which 0.077 per cent of alcohol had been added, when exposed to direct sunlight in colorless glass, began to decompose in 14 to 19 days. He found that after de- composition had been recognized by zinc iodid and starch, as well as by baryta water, reactions were obtained with 1:2000 potassium dichromate solution and the iodoform test, and these were ascribed to the presence of alcohol. Schacht (Ber. pharm-. Ges., Oct., 1894) defended his position, and stated that the reac- tions obtained were not produced by alcohol, but by "chloric ether" and "Phos- gene alcoholide. " The Browns {Pharm. J., 25, No. 3, 836) maintained that Schacht had not proved that ethyl chlorid and chloroformic ether are produced in the decomposition of alcohol-reduced chloroform, and that they give reactions similar to alcohol. On the other hand, they considered that they themselves had proved that at the time the decomposition is first recognized by means of zinc iodid and starch, chlorin has not been produced in sufficient quantity to com- bine with all of the added alcohol, and that ethyl chlorid, chloroformic ether, or carbonic ether do not give reactions which could be mistaken for those of alcohol. APPENDIX II 887 the decomposition products of chloroform containing alcohol were by no means definitely settled. Schoorl and Van den Berg^ conducted quantitative experiments which seemed to indicate that, when chloroform is decomposed by the ac- tion of light in the presence of an excess of oxygen, carbon dioxid, water, and chlorin are formed in accordance with the following equation : 2CHCI3 + 50 = 3CO2 + H2O + 3C1, According to the same chemists, when insufficient oxygen is present — a condition usually obtaining in practice — carbonyl chlorid and hydrogen chlorid are jDroduced in molecular proportions: CHCI3 + = HCl + COOL The equations given by Schoorl and Van den Berg were evidently in- tended to apply to the decomposition of pure chloroform, and the changes which occur in anesthetic chloroform were not, so far as we are aware, considered. Schoorl and Van den Berg^ confirmed the observa- tion that, in the absence of air or oxygen, chloroform is not affected by light exposure. Finally Dott ^ has suggested that the formation of carbonyl chlorid in chloroform very probably occurs in accordance with the following equation : CHCI3 + H2O2 = COCI2 + HCl 4- H.O * Baskerville and Hamor concluded from their experimental results that: (1) The products of the oxidation of pure chloroform are carbonyl chlorid and hydrochloric acid: CHCI3 4- H,0 + O2 = COCL + HCl + H2O2 ; CHCI3 + H2O2 = COCL + HCl -f H2O They were convinced that oxidation would not occur if water were excluded, and the absolute exclusion of moisture appears to be impossi- ble. Hydrogen dioxid is formed, although they were unable to detect it in chloroform undergoing oxidation, and therefore concluded that its ex- istence is ephemeral, and oxidation of the chloroform continues through- out the period of exposure. The decomposition of pure chloroform is favored by a degree of moisture, and is accelerated by light, as is shown by a comparison of the results obtained in the experiments wherein colorless glass was used with ^Pharm. WeeJcblad., 42, 877. 'Ibid., 43, 8. On exposure to air, in the absence of light, chloroform gave no precipitate with silver nitrate even after four hours, whereas bromoform and iodo- form after one hour gave distinct indications of decomposition. V. Soc. Chem. Ind., 27, 272. * Support to this view is had from the fact that conditions which favor the formation of hydrogen dioxid — a degree of moisture and direct sunlight — are also those which favor the decomposition of chloroform. 888 ANESTHESIA those in which anactinic glass containers were employed. Moreover, car- bonyl chlorid is always formed with increased readiness in the presence of acids. ^ The extent of the oxidation is dependent upon the nature of the con- tainer, the amount of air present, the purity of the sample, and the in- tensity of the light to which it is exposed. In light alone, when no air is present, no decomposition occurs for ordinary periods of exposure ; and in cases where there is air contact alone, and no exposure to light, the oxidation is slow. Free chlorin can only result from the photochemical decomposition of carbonyl chlorid:^ COCI2 = CO + CL It is likely that in the cases where "chlorin" was identified as an indica- tion of incipient alteration of chloroform hydrogen dioxid was the cause of the reactions observed. No chlorin was found by Baskerville when containers of anactinic glass were used. This view of the oxidation of pure chloroform is supported in full by the analogous case of the photochemical oxidation of iodoform,^ the pri- mary products of which are carbonyl iodid and hydriodic acid, free iodin resulting only from the decomposition of the carbonyl iodid and from the oxidation of the hydriodic acid. (2) The products of the oxidation of anesthetic chloroform are pri- marily the oxidation products of alcohol, and no decomposition of chlo- roform itself occurs while the oxidation of alcohol proceeds. When the oxidation of alcohol reaches a maximum, decomposition of the chloro- form goes on as in the case of pure chloroform, with the exception that chlorinated derivatives of the oxidation products of alcohol may result. The decomposition of the chloroform itself is retarded so long as oxida- tion of the alcohol proceeds, and the retardation is consequently depend- ent upon the amount of alcohol present, that is, the alcohol acts as a "negative catalyst" through its capacity for oxidation. The extent of the oxidation is, of course, subject to the conditions referred to as ap- plicable to "pure" chloroform. It is important to note, however, that ^ Lowry and Magson, Trans. Chem. Soc, 93, 121, who observed that the forma- tion of carbonyl chlorid is evidently accelerated by the presence of acids. "In this connection, see Coehn and Becker: Ber., 43, 130; and Weigert: Ann. Physik, 1907, S4, No. 4, 55. The influence of light on the reversible reaction, CO + Clj— ^^COCU, is purely catalytic. 'See Plotnikow: Z. physikal Chem., 75, 337, 385. According to this investi- gator the whole reaction is as follows: CHI3 + O = COI^ + HI; C0l2=:C0 + I,; 2HI + O = H,0 + I2. In the light, under constant conditions, the iodin separated is proportional to the time, and if the illumination is removed the reaction still proceeds, but with reduced velocity. There is no separation of iodin in the absence of oxygen, and none in a benzene solution which has not been exposed to light. APPENDIX II 889 anesthetic chloroform always contains water, the usual amount being about 0.05 per cent by volume, according to our experience. Verified Tests for Purity of Anesthetic Chloroform. — Odou. — Pure anesthetic chloroform possesses a characteristic odor,^ and such chlo- roform volatilizes entirely without disagreeable or foreign odor. The test may be carried out as follows: One hundred c. c. of anes- thetic chloroform are slowly evaporated over a water bath until about 10 c. c. remain in the flask. This residuum should be colorless and possess no foreign odor; and, when it is allowed to evaporate on fil- ter paper, there should result no odor of fusel oil, empyreumatic mat- ter, or other substances than chloroform and ethyl alcohol, as the last portions disappear. If a decided odor is imparted to the filter paper after the evaporation of the residue, or if any foreign odor is observed during the course of evaporation, the chloroform should be rejected; but for further information may be tested for such impurities as fusel oil, chlorinated derivatives of alcohol, acetone or the higher alcohols, ex- tractive matter, etc. Eesidue. — When 100 c. c. of anesthetic chloroform are allowed to evaporate in a platinum dish at -|- 100° C, there should be left no weigh- able residue. In every case this should be determined gravimetrically, and not by vision.^ Specific G-eavity. — The specific gravity gives a good indication of the strength of the preparation, that is, how much alcohol is present, and otherwise shows the purity of the drug to a much less degree. The determination should preferably be made with a pyknometer at -|- 15° C.^ Chloroform is very sensitive to temperature variation. The Mohr- Westphal balance will serve to give a rapid approximate result, but should not be depended upon where any considerable degree of accuracy is desired.* ^Passy (Compt. rend., 116, 769) made comparative experiments on the odorous power of chloroform, bromoform, and iodoform, which afforded the following sharp results in millionths of a gram: Chloroform 30.00 Bromoform 2 to 5 Iodoform 0.06 to 0.7 * White (Pharm. J., 25, No. 4, 540) proposed that when 10 mils of chloroform are allowed to evaporate in a clean glass beaker or dish, which is afterward heated on a water bath, there should be left no visible residue. * The form of pyknometer designed by Perkin (J. prakt. CJiem. N. F., SI, 486) is very suitable, although the Sprengel pyknometer is satisfactory. * Water. When 10 c. c. of anesthetic chloroform are agitated with 10 c. c. of paraffin oil (sp. gr., 0.880) there should be perfect solution and no turbidity pro- duced. This shows 0.1 per cent, but not traces, of water. The water per se is not objectionable, but its presence, provided air — that is, oxygen — is present, facili- tates decomposition in storage. For the detection of smaller amounts of water, use calcium carbid. See Baskerville and Hamor: Loc cit. 890 ANESTHESIA Okganic Impurities. — When 20 c. c. of anesthetic chloroform are mixed with 15 c. c. of concentrated sulphuric acid in a glass-stoppered vessel of 50 c. c. capacity which has been previously rinsed with concen- trated sulphuric acid, no visible coloration should be imparted to the mixture after the addition of 0.4 c. c. of pure 40 per cent formaldehyd solution, and then shaking throughout a period of five minutes.^ Acetone. — Anesthetic chloroform should give a negative reaction in all cases when the following exclusion test is applied: Ten c. c. of the sample are agitated with 5 drops of a 0.5 per cent sodium nitroprussid solution and 2 c. c. of ammonium hydroxid (sp. gr. = 0.925), and the mixture is then allowed to stand for several min- utes. Chloroform containing up to 1 per cent of alcohol may impart a yellowish brown color to the supernatant liquid on agitation, but when acetone is present an amethystine color results. This test must be con- ducted in the cold. After application to the suspected chloroform direct, the first 10 per cent distillate and the 10 per cent residuum obtained by allowing 100 c. c.^ of the sample to slowly distil should be tested. AcETALDEHYD. — When 10 c. c. of anesthetic chloroform are agitated with 10 c. c. of water and 5 drops of ISTessler's reagent U. S. P., and the mixture is then allowed to stand for 5 minutes, there should result no precipitate, and the reagent should assume no coloration, although it may become opalescent or slightly turbid. Acidity. — When 20 c. e. of anesthetic chloroform are thoroughly agitated with 10 c. c. of water and 2 drops of phenolphthalein solution, and then titrated with !N"/100 potassium hydroxid solution, added drop by drop, not more than 0.2 c. c. of standard alkali solution should be re- quired to produce a faint but decided alkaline reaction permanent for 15 minutes, when the mixture is shaken 30 seconds after the addition of each drop of alkali. If the presence of free acid is indicated, the sample should be rejected, but for further information may be examined for the oxidation products of pure chloroform (carbonyl chlorid, hydrogen chlo- rid) and alcohol. The Decomposition Products of Anesthetic Chloroform. — (a) The detection of acetaldehyd is referred to above; ^ The reasons for this test are given in full in the paper by Baskerville and Hamor: Loc. cit. *When the proportion of acetone to chloroform is 1: 500, the amethyst color is marked; but in the presence of 1 part in 1,000 the coloration is not distinct until the mixture of chloroform with ammonium hydroxid and sodium nitro- prussid has been saturated with ammonium sulphate, shaken, and then allowed to rest for five minutes. It is advisable, in all cases, to run a blank test on pure an- esthetic chloroform for comparison. Since acetaldehyd is generally present in fresh and properly stored samples of anesthetic chloroform in proportions greater than 1: 3300, usually the reaction is not interfered with by this substance; but in every case the sample should be examined for the presence of acetaldehyd. APPENDIX II 891 (b) Anesthetic chloroform failing to comply with the above acidity test, and which contains no carbonyl chlorid or hydrogen chlorid, should be rejected, since then the indication is that acetic acid is present; (c) When 20 c. c. of anesthetic chloroform are shaken during 20 minutes with 15 c. c. of concentrated sulphuric acid in a glass-stoppered tube of 50 c. c. capacity previously rinsed with sulphuric acid, and 2 c. c. are diluted with 5 c. c. of water, the liquid should remain colorless and clear, and should possess no odor foreign to anesthetic chloroform (chlo- roform and alcohol) ; and the liquid should still retain its transparency and colorless state when further diluted with 10 c. c. of water, and the transparency should not be diminished on the addition of 5 drops of sil- ver nitrate solution. A positive result is indicative of the presence of chlorinated derivatives of the oxidation products of alcohol, etc. Degrees of Purity of American Chloroforms. — The main impurities contained in American anesthetic chloroforms are, besides water, im- purities decomposable by sulphuric acid and traces of the oxidation products of ethyl alcohol. The presence of small amounts of ethyl alco- hol is necessary; but anesthetic chloroform should contain but mere traces of water, and it is desirable that it be absolutely water-free. The necessary precautions should be taken by manufacturers to guard against the presence of organic impurities as well as of extractive matter — a common contaminant of anesthetic chloroform contained in unprotected cork-stoppered bottles. The table (p. 893) will serve to show the comparative purity of various samples of chloroform. Nos. 1-9 were samples of anesthetic chloroform, supposed to be of the present U. S. P. grade and such as are now being supplied to the trade ;^ No. 10 was a sample, stated to be of U. S. P. quality, contained in a tin and 17 months old; ISTo. 11 was a sample of "Chloroform for Anesthesia" contained in a sealed tin, and 6 years old;^ and No. 12 was an unopened tin of "chloroformum purifi- catum," manufactured in 1863 or shortly before.^ The last two samples are of particular interest, since, so far as the aixthors are aware, they were the oldest samples of chloroform ever examined. ^All of these samples, with the exception of No. 6, were manufactured in the United States. These samples were obtained through the courtesy of the various manufacturers, to whom the authors desire to acknowledge their indebtedness. ^ Sample, dated Nov. 1, 1905, supplied by Surgeon-General Torney, U. S. A. ^ This sample was also furnished by Surgeon-General Torney who stated that this chloroform was taken out of a pannier of the variety issued during the Civil War, along with records, etc., which bore the date of 1863. To quote from his letter of transmittal, ' ' I presume that the chloroform was made at that period, or before, and I may say that it is the last survivor, so far as I know, of the chloro- form supplied at that period." It is important to note that this tin of chloro- form possessed a smaller air space than No. 11, the container being almost full; this accounts for the difference in oxidation of the alcohol in the two samples. COMPARATIVE PURITY OF VARIOUS SAMPLES OF CHLOROFORM All samples gave tests for water present in permissible amounts; negative acidity tests, U. S. P. negative tests for chlorides and for oxidation products of pure chloroform. No. Source. Grade. 1 Acetone Anaesthetic . . 2 Acetone Anaesthetic . . 3 Ansesthetic . . 4 Acetone AuEesthetic . . 5 Acetone Ansesthetic . . 6 Chloral Ansesthetic . . 7 Acetone Ansesthetic . . 8 Acetone Anaesthetic . . 9 Carbon tetrachloride . . . Ansesthetic . . 10 Ansesthetic . . 11 Acetone Ansesthetic . . 12 Alcohol Ansesthetic . . 13 Acetone Analytical . . . 14 Acetone Commercial. . Density at 25/25 Odor. Residue in gm, per Uter. 1.4827 Normal 1.4730 Normal None 1.4772 Normal None 1.4806 Normal None 1.4770 1.4839 Normal 1.4756 Normal 1.4750 Normal 1.4773 Normal 1.4751 Slightly pungent. . 0.0220 1.4722 Normal None 1.4747 Fruity 1.4752 Normal 0.0165 1.4846 Normal 0.0705 No. Extractive matter. Sulphuric acid test. Formalin- sulphuric acid test. 1 Present from cork Faint Faint brown . . . 2 Absent Negative .... Faint yellow . . . 3 Absent Negative. . . . Marked brown. 4 Absent Negative .... Negative 5 Absent Negative .... Brown color . . . 6 Present from luting .... Marked 7 Present from cork Decided 8 Indefinite Faint Very faint yellow 9 Trace Very faint . . . Faint yellow . . . 10 Trace Faint 11 Absent Marked 12 Present Pronounced 13 Present from cork Faint 14 Present Marked Absolute ethyl alcohol in c. c. per 100 c. c. 0.50 0.97 0.77 0.56 0.70 0.30 0.80 0.84 0.74 0.84 0.83 0.60 0.69 Higher alcohols. Not detected Not detected Not detected Not detected Not detected Not detected Not detected Not detected Not detected Not detected Present Propyl Not detected Not detected No. Acetone. Acetaldehyde. Acetic acid in gm. per 100 c. c. 1 Absent 0003 2 3 4 .5 Absent Not detected Not detected Trace. .. Trace . . . Trace . . . 0.0001 Absent 6 7 8 9 10 11 Not detected Not detected Not detected . . . Trace . . . . .. Trace.. . ... Trace . . . ... Absent. . ... Present . :3300 0.00015 0.00015 0.00030 Absent 0.00045 0009 12 1 : 2000 00045 13 14 Not detected Not detected Trace... . ... Trace... "Odorous "Chlorinated decomposition decomposition products." products." Absent Absent Absent Absent Absent Absent Absent Absent Absent Absent Faint reaction .... Trace Absent Very faint reaction Absent Present Absent Absent Absent Present Absent Present Present Absent Absent Faint reaction Absent Faint reaction 892 APPENDIX III OXYGEN History of Oxygen. Methods of Manufacturing Medicinal Oxygen. Impurities That May Be Present in Oxygen. Purity of Commercial Medicinal Oxygen. Standards of Purity That Should Be Eequired for Oxygen to Be Used in Medicine. History of Oxygen. — The alchemists^ were probably acquainted with oxygen, perhaps also the Greeks ^ in the fourth century, and the Chinese/ long before Priestley's experiments. In 1630 Jean Eey * knew that certain metals, when heated, fix a portion of the air, and in 1674 Mayow ^ prepared oxygen from niter. In 1771 Scheele ^ prepared a gas by heating several oxids, including the black oxid of manganese, and, at about the same time. Cavendish '^ studied oxygen. To Priestley,^ however, has been given the honor of discovering oxygen as a constitu- ent of the air. Davy ^ and Lavoisier ^° later studied the preparation and nature of this gas. Methods of Manufacturing Medicinal Oxygen. — At the present time there are the following methods of preparation and manufacture of oxygen :^^ ^Bolton: Am. Chem., 4, 170. ^Hoefer: "Histoire de la Chimie," 2, 271. 'Duckwood: Chem. News, 53, 250. * Jean Key : ' ' Essai sur la recherche de la cause pour laquelle 1 'airain et le plomb augmentent de poids quand on les calcine, ' ' Bazas, 1630. ® Mayow, Eodwell : Chem. News, 8, 113. ® Scheele : ' ' Chemische Abhandlung von der Luf t und dem Feuer, ' ' Upsala u. Leipzig, 1777. ^Cavendish: Trans. Boy. Soc., 56, 432; 74, 119, 170; 75, 372. » Priestley: Ibid., 62, 147; 65, 384; 73, 398; 75, 279; 78, 147, 313; 79, 7, 289; "Experiments and Observations on Different Kinds of Air," London, 1775-1777, 2, 29 ; 3, 1 ; " Experiments and Observations Eelating to Various Branches of Natural Philosophy," London, 1779, 1, 192. ^ Trans. Boy. Soc., 101, 1. ^"Crell: Chem. J own., 4, 440; 5, 125; Chem. Ann., 1786, 1, 33, 136; 1778, 1, 354, 441, 528, 552; 1788, 2, 55, 262, 431, 433; 1789, 1, 145, 162, 260, 323; 2, 68, 145, 433; 1790, 1, 69, 518; 1791, 1, 71; 1803, 1, 29. " Baskerville and Stevenson (/. Ind. Eng. Chem., 1911, 3, No. 7) made an elaborate investigation on this subject. For details of procedure and methods used, this paper should be consulted. 893 894 ANESTHESIA (1) Heating chlorates; (2) heating chlorates with various sub- stances; (3) from hypochlorites, and reaction of chlorin and water; (4) heating sulphuric acid or sulphates; (5) heating various solids and mix- tures. (MnOg, CuB^O^, etc.); (6) combustion of solid mixtures (chlo- rates with -combustible material, alkaline peroxids with hydrated salts, etc.) ; (7) reaction of peroxids ("oxone") with water and aqueous solu- tions; (8) by electrolysis of water; (9) from the air by means of mer- cury, cuprous chlorid, barium dioxid; manganates, plumbates, or living matter; dialysis or absorption; (10) from liquid air. For medicinal purposes oxygen is manufactured according to methods 3, 7, 8, and 10. Impurities That May Be Present in Oxygen. — The following sorts of matter may be suspected to exist in a cylinder of oxygen gas : (1) Solids; (2) liquids; (3) gases and vapors: HgO; halogen acids, HJSTOj, organic acids; O3, NOg, ^2^3, SOo; NH3, organic bases; CO2, halogens, oxids of chlorin; KCN, (CN),; PH3, SbHg, AsHg, H^S; H^; CO1CH4, organic matter; Ng? ^2^> rare gases of the atmosphere. If the method by which the oxygen has been prepared is known, a consideration of many of these impurities is unnecessary. For example, impurities M^hich exert a distinctly injurious physiological action are not to be suspected in oxygen prepared by electrolysis, liquid air, or the de- composition of alkaline peroxids (NagOa) by water. It is only neces- sary to know the percentage of actual oxygen present in the gas. This may be determined most conveniently, and with sufficient accuracy, by absorption in alkaline pyrogallate solution. Care should be taken to use an alkali produced electrolytically or HempePs^ precaution to prevent the production of carbon monoxid. Nitrogen and the inert noble gases of the air are determined by difference. Purity of Commercial Medicinal Oxygen. — One of us (C. B.)^ has devised elaborate methods for the examination of oxygen and determined the purity of "C. P." oxygen offered on the market for medicinal use. Below is given a tabulation of the results of analyses, according to these methods, of seven makes of oxygen. Organic N2 All other fo. Source of oxygen O2 H2O CO2 H2 Matter etc. impurities. 1 KCIO3 + MnOj 93.20 0.30 0.11 6.39 2 KCIO3 + Mn02 98.31 0.14 present 1.54 3 KCIO3 + MnOz 92.82 0.26 trace 6.92 4 KCIO3 + Mn02 97.13 0.23 present trace 2.63 5 Liquid air 96.10 0.15 0.01 3.74 6 Electrolysis 99.23 0.35 9.03 0.14 0.25 7 Na202 +H2O 99.20 0.50 trace 0.30 These were all medicinally pure. *"Gas Analysis," English translation by Dennis, 1906, 149. ^ In conjunction with Stevenson, loc. cit. APPENDIX III 895 Standards of Purity That Should Be Required for Oxygen to Be Used in Medicine. — The gas should be neutral toward moist, delicate litmus paper (showing absence of irritating acid or alkaline gases) ; and, when passed through an aqueous solution of silver nitrate, it should pro- duce no turbidity (absence of chlorin or chlorin oxids). Not more than an opalescence should be produced when 2 liters of the gas are passed slowly through an aqueous solution of barium hydroxid (showing mini- mum of carbon dioxid). This condition is to be modified when a mix- ture of oxygen and carbon dioxid (4 per cent of the latter) is deliber- ately used. See Chapter II. When 5 liters of the gas are passed slowly through an aqueous solution of sodium hydroxid, then over heated cop- per oxid, and finally through an aqueous solution of barium hydroxid, no turbidity should be produced (showing absence of organic impurities, as hydrocarbons). The gas should contain at least 95 per cent oxygen upon the dry basis. As supplied for use, the gas should contain no liquids and no solids. INDEX Abdomen, effect of shock on, 385 ether irrigation of, 672-674 local anesthesia of, 516-519 Abdominal distention, effect of re- breathing on, 113 in colonic ether anesthesia, 436 Abdominal operations, shock in, 403 under anoci-association, 407 under chloroform, 314 under local anesthesia, 488, 519 under spinal analgesia, 560, 586, 587, 597 site of injection for, 612 Abdominal spasm during anesthesia, 381 Abernathy on the anesthetist as a spe- cialist, 676 Abortion, due to electric analgesia, 635 Abraham, on purification of chloro- form, 878 Abscess of the lung, anesthesia in, 329 oral, injection into, contra-indicated, 546, 547 A. C. mixture, Sansom's, 809, 810 Schafer and Scharlieb's, 810 Acapnia, 406-409 as cause of death under ether anes- thesia, 193 as cause of shock, 401. See also Vasomotor activity prevention of, 112, 409 A. C. E. mixture, 688, 689, 703 administration of, 142 early use of, 23 statistics for, 843, 855 Acetaldehyd, 689 in chloroform, 286, 890 in ether, 866, 867 Acetate lactic in spinal analgesia solu- tion, 603 Acetic acid, impurities in ethyl chlorid due to, 253 in chloroform, 285, 286, 891 Acetic ether, 736. See also Ethyl ace- tate Acetoform, 689 Acetone, 689 methods of testing chloroform for, 890 preparation of chloroform from, 285, 874, 875, 882 Acetone-chloroform, 724, 772. See also Chloretone and Methaform Acetonuria, after ether anesthesia, 198 See also Chloroform poisoning 897 Acetyl chlorid, presence of, in ethyl chlorid, 253 Acetylene, 689, 690 Acetylene dichlorid, 733 See also Dioform Acetylene tetrachlorid, 831. See Tet- rachlorethane Acid intoxication due to ether, 413 post-anesthetic, 70 symptoms of, 415 treatment for, 414 See also Chloroform poisoning Acids, method of testing chloroform for, 890 method of testing ether for, 866 Acidum amidobenzoicum aethylatum. See Anesthesin Acoin, 540, 690, 691 in spinal analgesia, 563, 599 Acoincocain. See Acoin Acoin oil, 691 Acoinol, 691 Adenoid and tonsil cases, 340-352 after-treatment of, 345 anesthesia in, 341 death due to unskilful anesthesia in, 336 nasal nitrous oxid-oxygen anesthesia in, 173 results in, due to lack of preliminary medication, 369, 370 sequestration-anesthesia in, 470, 474 technique of, 344, 345 upright position for, 345-352 use of ethyl chlorid in, 268 use of nitrous oxid in, 140 Adenoid operations, ether in, 247 under oil-ether colonic anesthesia, 465 use of Junker apparatus in, 322 A-diehlorethane, 750 Adralgin, 691 Adralgin chirurgicum, 691 Adralgin dentale, 691 Adrenalin, 691, 692 combined with novocain, in dental anesthesia, 540-542 in anesthesia of scalp, 497 in local anesthesia, 478 in preparation of cocain solutiona, 539, 540 in spinal analgesic solutions, 576, 599 with chloroform, 373 with cocain, 480, 481, 691 898 INDEX Adrenalin hydrochlorid in spinal anal- gesia, 601 Adrenalin-Kokain-Tabletten, 691 Adrenals, effects of cldoroform on, 304 Adrenin with saline in shock preven- tion, 403, 404 Adrian" on decomposition of chloro- form, 885, 886 Adrecain, 691 Adrin and cocain tablets, 691 Aeration of lungs during anesthesia, 376 -^ther anaestheticus aranii, 691, 692 j^ther aneestheticus Kiinig, 691 Mther anaestheticus Wiggers, 692 ^ther chloratus. See Ethyl chlorid JEther hydrocJiloricus seu muriaticus, 250. See also Ethyl chlorid ^ther pro narcosi, 861 ^ther purificatus, 861 ^ther vitrolique, 860 ^tho-methyl, 692 ^thoxycaffein, 692 -^thylenum ehloratum. See Ethylene chlorid ^thylis aminobenzoas, 737, 738 ^thylium amidobenzoicum. See Anes- thesin ^thyloform, 692 jiEthylum ehloratum, 250. See also Ethyl chlorid After-treatment for adenoid and tonsil cases, 345 in intravenous anesthesia, 530-532 in oil-ether colonic anesthesia, 463 in ordinary cases, 378, 379 Age in relation to spinal analgesia, 591 in resistance to surgical shock, 383, 384 influence of, in hypnotism, 655 selection of anesthetic with regard to, 326-328 Aged, ethyl chlorid anesthesia in, 268 nitrous oxid anesthesia contra-indi- cated in, 136 Air, administration of nitrous oxid with, 142, 143 in definite amounts, 141 in unknown quantities, 140, 141 as an anesthetic, 692 as vehicle in colonic ether anesthesia, 452 comparative value of oxygen and, 81, 82, 83 effect of, on chloroform, 290, 883- 889 ethyl chlorid and, 276 insufflation of, as a method of arti- ficial respiration, 432 following intratracheal anesthesia, 429 preparation of oxygen from, 894 Air passages, obstruction of, in nitrous oxid-oxygen anesthesia, 168 Airway, artificial, in surgical anes- thesia, 390 ■ Airway, free, method of maintaining, 361, 362 maintenance of, by artificial respira- tion, 393 in intravenous anesthesia, 529, 530 with breatliing tubes, 390, 392 obstruction in, due to shock, 389 open, maintenance of, in ether anes- thesia, 233 Albuminuria, absence of, in ethyl chlorid anesthesia, 265 in anesthesia, 61 in ether narcosis, 190 post-chloroformic, absence of, follow- ing sequestration anesthesia, 472 Alcohol as preservative of chloroform, 283, 285, 290, 291, 295 in A. C. E. mixture, 688, 689 in anesthetic block for shock preven- tion, 406 in ether, oxidation of, 182 in preparation of chloroform, 873, 874 in preparation of ether, 860, 861, 862 in preparation of ethyl chlorid, 252 in spinal analgesic solutions, 599, 603 presence of, in chloroform, 878 preservative influence of, on chloro- form, 886 test for, in ethyl chlorid, 257 Alcohol oxidation in chloroform agita- tion, 296 Alcohol phenicum. See Carbolic acid Alcohol trichloramidoethylique. See Chloralformamid Alcoholic muriatic ether, 251 Alcoholics, administration of nitrous oxid in, 140 choice of anesthetic in, 329 colonic ether anesthesia in, 437 ethyl chlorid anesthesia in, 262, 269 oil-ether colonic anesthesia for, 461 preliminary medication in anesthetiz- ing, 371, 372 sequestration anesthesia in, 473 under spinal analgesia, 626 use of ethyl chlorid, ether, and oxy- gen in, 278 Aldehyd in anesthetic ether, 183, 869 in chloroform, 285 Aldehyds, compounds of, with hydrogen chlorid, 253 Alden's auto-operation under spinal analgesia, 580 Alessandri on postoperative effects of stovain analgesia, 582, 583 Alexander and Gwathmey on adenoid and tonsil cases, 340-352 Alimentary lesions, colonic ether anes- thesia contra-indicated in case of, 457 Alimentary tract, effect of nitrous oxid on, 132 Allen, on "methylated chloroform," 874 INDEX 899 Allen, on methylated ether, 861 Allis ether inhaler, 216 Allocain, 692 Allopathy and homeopathy, 678 " Alpha-eucain, " 751-753 Alphachloralose, 723 Alvatunder, 692 Alypin, 540, 691-696 action and uses of, 693 dosage for, 693 formation of, 692, 693 in spinal analgesia, 563, 585, 599 Alypin-Gleitmittel, 696 Alypin nitrate, 696 Alypin-Tabletten, 696 Alypinoids, 696 American Painless Dentists' Anes- thetic, 696 American statistics on anesthesia, 843, 853-856 Amidin. See Holocain hydrochlorid Amido-oxybenzoic acid methyl ester, 772 Aminobenzoic acid ethyl ester. See Auesthesin Aminobenzoic acid isobutyl ester. See Cycloform ^minobenzoyldiethylaminoethanolum hy- droehloricum. See Novocain Aminocinnamic acid alkamine esters, 697 Ammonia administration in respiratory failure, 396 with chloroform, 287 Ammonium hydroxid, in testing chloro- form, 890 Ampules solution atoxyl, 10 per cent, with novocain, 1 per cent., 697 Amputation of arm under local anes- thesia, 506, 507 of breast under colonic ether anes- thesia, 454 of foot under spinal analgesia, 578, 625 under intravenous anesthesia, 492 Amydricain, 697 Amyl in chloroform, 285 Amyl alcohol, impurities in ethyl chlorid due to, 253 Amyl chlorid, 697, 698, 718 Amyl hydrid, 748, 767, 802 Amyl nitrate, 698 as an antidote to cocain poisoning, 479 in respiratory failure, 395 use of, in anemia of the brain due to cocain, 539 Amyl salicylates as preservative of chloroform, 292 Amylene, 698, 699 Snow's first administration of, 23 Amylenechloral, 699 Amylocain, 699 Aneesthesin bormelin, 702 Ansesthesin solubile, 702 Ana;sthesinum solubile, 829. See Sub- cutin Ansesthesinum sulfophenylicum. See Subcutin Anspsthetica Tabletten, 702 Anajstheticum, 702 AnEestheticum Bottwini, 702 Ana3stheticum Witte, 702 Anapsthin and anassthol, 702 Anffisthol, 702-710 Ansesthol Katz, 702 Ansesthyl, 710 Anajsthyle. See Anagsthol Ansestiform, 710 Anajzol, 710 Analgos, 710 Andolin, 710 Andrews, E., nitrous oxid and oxygen mixture by, 24 Anelectrotonus, 51 Anemia, choice of anesthetic in, 328, 329 of the brain, due to cocain, 539 due to electric shock, 637 in sequestration anesthesia, 469 sequestration anesthesia contra-indi- cated in, 470 surgical shock and, 384 Anemic subjects, ethyl chlorid anes- thesia in, 268 gastro-enterostomy in, 356 Anemogenol, 699 Anemorenin, 699 Anesin, 711, 724 Aneson. See Anesin Anesthaine, 711 ' ' Anesthesia dolorosa, ' ' 479 Anesthesin, 699-702 Anesthesin sulphophate. See Subcutin Anesthesine in spinal analgesia, 563, 599 Anesthetics, antagonism between salts and, 55 combination of oxygen with, 80-89 effect of moisture on, 76-80 effect of, on circulatory system, 57- 59 on glandular system, 60, 61 on muscular system, 59, 60 on nervous system, 61, 62 on respiratory system, 56, 57 intra-abdominal administration of oxygen in connection with, 89- 91 list of, 688-840 rebreathing in administration of, 100-116 use of carbon dioxid with, 96-99 use of oil of bitter orange peel pre- ceding administration of, 91-96 warming, 63-76 Anesthetist, duties of, 361, 362 kit of, 362, 363 Anesthetist, laws relating to, 686, 687 liability of, 684 medico-legal status of, 675-687 900 INDEX Anesthetist, qualifications of, 675 Anesthia. See Anesthsesin Anesthol, 208, 276-278, 702, 711. See also AniBsthol chloroform and, 857 in operations for cleft palate, 340 statistics for, 843, 848, 855, 857 use of, in children, 328 in heart disease, 329 Anesthol-chloroform, statistics for, 843, 855, 857 Anesthol-ether-chlorof orm, statistics for, 843, 855 Anesthol-ether sequence by the drop method, 208, 209 for patients between 19 and 50, Statistics for, 843, 847, 855, 857 Anesthol-nitrous oxid, statistics for, 856 Anesthol-oxygen, safety of, 325 statistics for, 843, 856 Anesthone-Creme, 711 Anesthone-tape, 711 Anesthyl, 537 Anestile, 537, 711 Anestol, 711 Anestyle. See Ansesthol Anestyle-bengue. See Anestile Aneurysm, chloroform indicated for, 310 ether contra-indicated in, 248 Angina, dysphagin in treatment of, 735 Angina Ludovici, anesthesia in, 353, 354 Angina pectoris, nitrous oxid and oxy- gen in treatment of, 670 Angiomata of abdominal wall, opera- tion on, under spinal analgesia, 625 Anhydroglucochloral, 723 Anoci-association, 370, 388, 405, 463 operations under, 406, 407 Anodyne. See Ethyl chlorid Anodynone, 250. See also Ethyl chlorid Anorectal surgery, eucain lactate in, 758 Anschiitz salicylid chloroform, 877 Antemesin, 711 Anterior teeth, technique of periosteal injection of anesthetic solution about, 545 Anthrax, aeoin in, 690 Antidolorin, 250, 537, 712. See also Ethyl chlorid Antipyrin, 712 Antivom, 712 Antrum of Highmore operations, an- esthesia in, 340 Anus, anesthetization of, 514-516 effect of shock on, 386 site of spinal puncture for, 610 Apinol, 712 Apnea in anesthesia, 57, 298, 308, 380, 408, 409 Apoplexy, electric analgesia contra-in- dicated in, 635 Apotheker Maier 's Radikal-Anastheti- kum. See Radikal-Anastheti- kum Apparent death, electric resuscitation in, 636-643 Appendectomy, shock in, 412 under colonic ether anesthesia, 454 under local anesthesia, 518, 521 under spinal analgesia, 580, 581, 589 Appendicostomy, open, colonic ether anesthesia contra-indicated in, 457 Aran's anesthetic ether. See .^ther Anaestheticus Aranii Aran's ether, 691, 750 Arm amputations under local anes- thesia, 506- 507 Arnold's dental anodyne, 713 Arnott, iga packs advocated by, 537 Aromatic spirits of ammonia in chloro- form administration, 313, 316 Arsenic trioxid, 759 d 'Arsonval, anesthetic property of high- frequency currents discovered by, 628 Arterial anesthesia, 492, 493 Arterial injection in local anesthesia, 478 Arterioles, effect of ethyl chlorid on, 259 Arteriosclerosis, sequestration anes- thesia contra-indicated in, 470 Artificial respiration, 83, 86, 463 apparatus for induction of, 396 by insufflation of pure air or air and oxygen, 432 following use of cocain, 539 in ethyl chlorid anesthesia, 267 in oil-ether colonic anesthesia, 462 in status lymphaticus, 334 in treatment of acapnia, 409 in treatment of shock, 393-403 by Draeger's pulmotor, 396-399 by Lewis "pendulum swing," 393- 396 by lung motor, 399 by manual means, 393 by Meltzer's apparatus, 399-401 Asphyxia and shock, 388 death due to, in ethyl chlorid anes- thesia, 261 in nitrous oxid anesthesia, 844 in status lymphaticus, 333 due to nitrous oxid, 127, 132, 134, 136, 137, 154 symptoms of, 137 due to nitrous oxid and oxygen, 845 in ether anesthesia, 189 prevention of, in ethyl chlorid-oxy- gen anesthesia, 278 symptoms of, during anesthesia, 363 INDEX 901 Asphyxiation of tissues in anesthesia, 49 Asphyxiation theory of nitrous oxid action, 124, 125 Asthma, anesthesia in, 330 chloroform indicated for, 310 ether contra-indicated in, 248 ether treatment for, 4, 176 eupnea in treatment of, 760 spinal analgesia in, cases of, 586 Atheroma, ether contra-indicated in, 248 sequestration anesthesia contra-indi- cated in, 470 Atheromatous conditions, choice of anesthetic in, 328 Athletes, administration of nitrous oxid in, 140 choice of anesthetic in, 329 ethyl chlorid anesthesia contra-indi- cated in, 269 oil-ether colonic anesthesia for, 461 preliminary medication in anesthetiz- ing, 371, 372 Atoxyl and novocain, 818 Atropin, 463, 464, 465, 688 administration of, during anesthesia in status lymphaticus, 334 as preventive of cardiac inhibition, 402 in acute mania, 669 in preliminary medication, 371, 373, 461, 612 in respiratory failure, 394 in shock prevention, 402 omission of, in post-operative treat- ment, 378 preceding adenoid and tonsil opera- tions, 341 preceding anesthesia, 328, 329, 331 preceding intratracheal anesthesia, 427 preceding nitrous oxid-oxygen anes- thesia, 165 with ethyl chlorid, 373 Atropin sulphate in intravenous anes- thesia, 524 Automatic closing tubes for ethyl chlorid, 254, 255 Auto-observations under spinal anal- gesia, 577, 580, 581 Avamresco's sites for spinal puncture, 610 Axillary adenitis under colonic ether anesthesia, 454 Axillary glands, enlargement of, in status lymphaticus, 332 Babcock on spinal analgesia, 581, 583, 595, 612 on cerebrospinal fluid diffusion in, 568, 569 on solution for, 603 on technique in, 587, 622, 623 Babcock 's needle for spinal analgesia, 615 Baglioni's theory of anesthesia, 46, 47 Bainbridge, W. S., on spinal analgesia and spinal anesthesia, 554-627 Bainbridge 's method of cocain steri- lization, 605 of intra-abdominal administration of oxygen, 89, 90 of spinal analgesia, 600, 604 Bandages, cutting of, preceding anes- thesia, 337 Bandaging in arterial anesthesia, 492, 493 in shock prevention, 403 in venous anesthesia, 490-492 Barium hydroxid in testing purity of oxygen, 895 Barker on adrenalin, 478 on spinal analgesia, 567, 568, 571, 590, 591, 592, 602 Barker's anesthetic, 713 Barker's experiments, on cerebrospinal fluid diffusion, 568 with stovain injection in spinal anal- gesia, 571, 572 Barker's solution for spinal injection, 568, 569, 579 Barker's stovain-glucose solution for spinal analgesia, 602, 603 Baskerville, experiments of, on effect of moisture on anesthetics, 76, 77 investigations of, on storage of ether, 868 on heat generated by chloroform- ether mixture, 706-710 Baskerville and Gwathmey, experi- ments of, on warming ether vapor, 71-73 Baskerville and Hamor, on decomposi- tion of chloroform, 887-889 Battelli, experiments of, on electric re- suscitation, 637 Baume, ether manufactured by, 860 Behr on ethyl chlorid anesthesia, 267 Benesol, 713 Bengue's mentholdragees, 713 Bennett's nitrous oxid-ether apparatus, 218 Benzcain, 713 Benzene, 284, 713, 714 Benzenaform. See Carbon tetra- chlorid Benzin, 721 in Schleich's mixtures, 703, 704 Benzineroid. See Carbon tetrachlorid Benzinof orm. See Carbon tetra- chlorid Benzoylaminoethanol, 714 Benzoyl - beta - hydroxy - tetramethyl- pyrrolidin, 714 Benzoyl-ecgonin-methyl-ester, 725 Benzoyl - ethyl-dimethylamino-propanol- hydrochlorid, 819. See also Stovain Benzoyl methyl triacetonalkamine, 715 902 INDEX Benzoyl morphin, 715. See also Peronin Benzyl-morphin hydrochlorid, 802 Benzoyl peroxid, 714 Benzoyl quinin, 715 Benzoyl vinyl diacetonalkamin. See -Eucain-B. Benzoylpseudotropein, 833. See also Tropacocain Benzoylpseudotropein hydrochlorid, 832 Benzoyl - triacetone - alkamin - car- boxyl, 714, 715 Benzoyl-tropein, 715 Bernard, Claude, on chloroform, 26 theory of anesthesia advanced by, 34 use of morphin hydrochlorid by, 779 Bert on nitrous oxid anesthesia, 126 Bert's apparatus for nitrous oxid and oxygen, 24 Bertel on chloroform and oxygen, 26 Berzelius on chloroform, 873 theory of etherification advanced by, 862 Beta - benzoyloxy-beta-3 :4-methylenedi- oxyphenyletlvyldimethylamin, 715 Beta- ethyletramethyldiaminoglycerin benzoyl monochlorid, 715 Beta-eucain. See Eucain-B. and epinephrin, statistics for, 842 in spinal analgesia, 563, 599 Beta-eucain hydrochlorid, 756 Beta-eucain lactate in spinal analgesia, 563, 599 Beta - gamma - dibenzoyloxy - dimethyl- propylamin, 715 Beta-isoamylene, 801, 802. See Amy- lene Betacain. See Eucain-B. Beven on acid intoxication due to anes- thetics, 414 Biberfield, experiments of, vvfith novo- cain-adrenalin, 540 Bicarbonate of potash in preliminary treatment of kidneys, 364 Bichlorid of ethidene introduced by Clover, 25 "Bichlorid of methylene," introduc- tion of, 24 Bichlorid solution dish, 615 Bier on spinal analgesia, 559, 560, 562, 563, 567, 568, 602 method of, 755 Bier's method of local anesthesia, 490- 492 arterial injection in, 478 in hernia, 521 . limitations in use of, 586 stovain solution for, 602 tropacocain solution for, 601 of thyroid surgery, 503, 504 of venous anesthesia, 490-492 Bigelow, Jacob, on Morton, 14 rhioglene introduced by, 808 Billroth 's mixture, 689 Billroth 's mixture A. C. E., 715 Biltz on chloroform Pictet, 880, 881 Binz's theory of anesthesia, 34 Bitter orange peel. See Oil of bitter orange peel Bivalent carbon hypothesis, 42, 43 Black bear's foot, 764 Bladder, anesthesia of, with antipyrin, 712 care of, preliminary to anesthesia, 364 local anesthesia of, 512, 513 Blake cone, 102 Bleaching powder, in preparation of chloroform, 873 Bloch on the effects of ether upon the _ blood, 187 Blocking the cervical plexus in goiter operation, 503 in surgery of neck, 501 line of stitches, dosage for, 406 Blood, action of chloroform upon, 298- 301 effect of anestheti'?s on, 57-59 effect of ether upo.n, 185-188 effect of nitrous oxid on, 128-130 in stools under colonic ether anes- thesia, 455 Blood changes in intravenous anes- thesia, 533, 534 Blood pressure and shock, 383, 384, 410-413 during oil-ether colonic anesthesia, 463 effect of abdominal pressure on, 401 effect of anesthetics on, 59 effect of ethyl chlorid on, 259, 260 effect of nitrous oxid on, 130, 131 in chloroform-oxygen narcosis, 87 in ether-oxygen narcosis, 87 in intravenous anesthesia, 533, 534 in nitrous oxid-oxygen anesthesia, 166, 167 in operations under Crile 's method, 402, 403 in spinal analgesia, 581, 595 increase of, in shock prevention, 402- 404 relation of, to respiration in ethyl chlorid anesthesia, 259 Blood-pressure apparatus of McKeson, 409, 411 Bloodless field for adenoid and tonsil operations, 344, 345 ' ' Bloodless ' ' operations with electric analgesia, 634 Blue light, as an anesthetic, 715 Blumdell, ice packs advocated by, 537 Bodine's tubes of cocain solution, 482 Body weight, loss of, following ethyl chlorid anesthesia, 265 Bonain, 715 Bonawische mixture. See Bonain Bone resection under local anesthesia, 512 Boothby, on warmed ether vapor, 73-75 INDEX 903 Boothby and Cotton apparatus for ni- trous oxid-oxygen anesthesia, 160-170 Boothby and Cotton face mask for nitrous oxid-oxygen anesthesia, 166 Boro-chloretone, 716 Borsain, 716 Bottger, preparation of chloroform from acetone by, 874 Boullay, manufacture of ether by, 860 Boyle on ethyl chlorid anesthesia, 267 Brain, effect of anoci-association on, 370 effect of chloroform on, 301 effect of shock on, 384 examination of, under local anes- thesia, 496 Brain cell changes under nitrous oxid anesthesia, 404, 405 Brain cell exhaustion under ether anes- thesia, 404, 405 Brain surgery, anesthesia in, 354 chloroform indicated for, 310 sequestration anesthesia indicated in, 469, 470 Bramwell, on advantages of hypnotism in anesthesia, 647 method of inducing hypnosis em- ployed by, 657 Brandwundenol, 716 Braun, experiments of, with novocain- adrenalin, 540 formulas of, for cocain solutions, 481, 482, 489 on adrenalin, 478 on eucain-B, 755, 756 on layer infiltration, 503 on local anesthesia in hernia, 521 Braun 's inhaler for chloroform-ether administration, 323 Braun 's method for circumcision, 514 for thyroid operations, 503 in local anesthesia of skin, 495, 496 Braun 's novocain-suprarenalin solution for spinal analgesia, 603, 604 Braun 's solutions for anesthesia, 716 Braun 's suprarenin tablets, 716 Breast, amputations of, under colonic ether anesthesia, 454 carcinoma of, under oil-ether colonic anesthesia, 465 Breast surgery under local anesthesia, 505, 506 Breathing. See Eespiration Brenz eatechin methyl-benzyl ether. See Brenzcain Brenzcain, 716 British Pharmacopoeia, ethyl chlorid tests prescribed by, 257 Bromaform, 717 and ethyl bromid, 853 Bromal, 717 Bromic ether, 738-748. See also Ethyl bromid Bromids in preliminary medication, 329, 371, 653 for spinal analgesia, 612 Bronchi, effect of nitrous oxid on, 128 Bronchitis, anesthesia in, 330 chronic, spinal analgesia in, 586 ether contra-indicatnd in, 342 post-anesthetic, caused by ether, 189 Brown on decomposition of chlorofo"rm, 885, 886 Brucin, 717 Briining on effect of moisture contents of air on lungs, 78-80 on value of oxygen with narcotics, 83, 86 Brunn on mode of action of nitrous oxid, 126 Brunton, Lauder, on chloroform, 26 Briistlein on pantopon, 799 Biinte and Moral's local anesthetic, 717 Burckhardt on intravenous anesthesia, 524 Biirker's theory of anesthesia, 48 Busse on spinal analgesia, 595 Butyl alcohol, impurities in ethyl chlorid due to, 253 in chloroform, 285 Butyl-chloral hydrate, 718 Butyl chlorid, 718 Butyl hydrid, 718 Butylene, 689 Buxton on effect of nitrous oxid on the blood, 128 on ethyl chlorid anesthesia, 260 on limitations in use of spinal anal- gesia, 586 on rectal etherization, 435 Buxton 's apparatus for ether adminia- tration per rectum, 441 Byasson on formic ether, 748 Cachexia, intratracheal insufflation in, 432 Cactin, hyoscin, and morphin, 768 Cadet on ether, 860 Caglieri on spinal analgesia, 560, 561, 562, 565, 566 Calcium chlorid, chloroform dried over, 878, 879 Calcium guaiacol sulphonate. See Guaiacyl Calculi, renal or biliary, passage of, anesthetic treatment for, 667 Camphor phenylated, 718 Camphorated oil administration in res- piratory failure, 396 Camphorated salol. See Salol camphor Canadol, 718 Cancer, anesthesia in, 330 Canestro, use of magnesium sulphate by, 771 Cannula for Bier's venous anesthesia, 491 for spinal analgesia, 614, 615 introduction of, in intravenous anes- thesia, 527 904 INDEX Cantelupe, on action of ethyl chlorid, 261 Caprylic hydrid, 718 Carbamidum, 805 Carbolic acid, 718, 719 Carbon dioxid, 719 early use of, 2 effect of, in rebreathing, 111, 112 on arteries and veins, 114 on intestines, 114, 115 for restoration of respiration, 463 in dental anesthesia, 537 in oil-ether colonic anesthesia, 462 loss of, in shock causation, 406-408 physiological role of, 96, 97 reduction of, in the blood by chloro- form, 298 causes of, 97, 98 effects following, 97 use of, with anesthetics, 96-99 Carbon dioxid snow, 537 Carbon disulphid, 719, 720 removal of, from carbon tetrachlorid, 883 Carbon monoxid, 720 Carbon tetrachlorid, 720, 721, 883 preparation of chloroform from, 285, 875, 876 Carbonyl chlorid as product of pure chloroform decomposition, 290 in chloroform, 286, 884, 885, 887, 888 Carcinoma, acidosis in, 415 of superior maxilla, operation for, und«r spinal analgesia, 574 Carcinomatous gland case, results in, due to lack of preliminary medi- cation, 370 Cardiac arrest due to chloroform, 386 _ Cardiac cases, use of rebreathing in anesthetizing. 111 Cardiac massage following chloroform poisoning, 642 in ethyl chlorid anesthesia, 267 in status lymphaticus, 334 Cardiac syncope due to chloroform, 305, 306 Carlson and ethyl chlorid, 27 on chloroform, 299 Carotid arteries, compression of, 467, 468 Carotid gland, sequestration anesthesia for removal of, 471 Carpophyllic acid. See Eugenol Castor oil in preliminary treatment, 365, 461 Catarrh, eugallol in treatment of, 759 formaldehyd-kelene in treatment of, 760 of upper air passages, ether contra- indicated in, 342 Cathartics, use of, preceding adenoid and tonsil operations, 340 Catheters, rubber, for removal of blood, in adenoid and tonsil operations, 345 Catheters, tracheal, for intratracheal insufflation, 425, 426, 430 introduction of, 426-429 Caustica, 721 Cavendish, oxygen studied by, 893 "C. E." mixture, 81, 721 Hewitt's, 764 safety of, 325 statistics for, 843, 855 use of, in children, 327 in heart disease, 329 with air, safety of, 325 C. E. mixture-ether-chloroform sequence, 326 C. E. mixture-ether sequence, 326 Ceratum odontalgicum, 721 Cerebellar tumor, excision of, under se- questration anesthesia, 469 Cerebral diseases, convulsions from, ni- trous oxid-oxygen in, 667 Cerebrospinal fluid, diffusion of, 565- 572 escape of, on puncture, 618, 619, 621, 622 in spinal analgesic solutions, 599, 600 physiology of, 563-572 specific gravity of, 565 Cerebrospinal meningitis, death due to status lymphaticus in, 335 Cervical laminectomy under colonic ether anesthesia, 454 Cesarian section under spinal analgesia, 593 Chancel's theory of etherification, 863 Chaput on spinal analgesia, 562, 575, 598 on stovain solution for, 602 Charlatanism, hypnotism and, 649 Charme, 654 Chassaignac cocain in, on spinal anal- gesia, 600 Cheeks, operations on, under local anes- thesia, 497 Chelen, 250, 722. See also Ethyl chlorid and Kelene Chemicals and psychic shock, 384 Chemistry of chloroform, 281-297 Chest dissections, shock in, 402 Chest operations, colonic ether anesthe- sia indicated in, 457 Chevanne's local anesthetic, 722 Chiene on death due to spinal anal- gesia, 597, 598 Children, administration of nitrous oxid-oxygen in, 143 anesthetic treatment for convulsions in, 667 and shock, 387 ether contra-indicated for, 248 hypnotism in, 655 importance of psychic influences in anesthetizing, 651 nitrous oxid anesthesia contra-indi- cated in, 135, 136 oil-ether anesthesia for, 462, 465 INDEX 905 Children, use of ethyl chlorid anesthesia in, 268 use of spinal analgesia for, 561, 588 Chininum bihydrochloricum, 805 Chipman on the term ' ' anesthetist, ' ' 676 Chlorabutanol, 772 Chlora3thoform, 722 Chloral, 691, 722 Chloral-acetone chloroform, 722 Chloral chloroform, 876, 877 Chloral-menthol, 723 Chloral-orthoform, 723 Chloralamid. See Chloralformamid Chloralformamid, 723 Chloralimid, 723 Chloralose, 723 Chloramyl, 723 Chloran. See Chloral-acetone chloro- form. Chlorates, preparation of oxygen from, 894 Chlorbutane, 723 Chlorbutanol. See Chloretone and Methaform Chlorbutol. See Chloretone. Chlorethyl. See Ethyl Chlorid Chlorethylene chlorid. See Ethylene Chlorethylidene. See Ethylidene chlorid Chloreton, 724 Chloretone, 463, 464, 465, 711 in postoperative treatment, 378 in preliminary medication, 371 for oil-ether anesthesia, 460, 461 use of, preceding adenoid and tonsil operation, 341 Chloretone and morphin, doses of, in preliminary medication, 372 "Chloric ether," 872 Chlorid of lime in preparation of chloroform, 285 Chloriden. See Ethylidene chlorid Chloridene, 750 Chlorin, action of, on ethyl iodid, 252 as product of pure chloroform de- composition, 290 formation of, on exposure of chloro- form to air, 883-888 in chloroform, 286, 875 in preparation of oxygen, 894 Chlorinated muriatic ether, 750 "Chlorinated" oils in chloroform, 285 Chlorojethyl, 250. See also Ethyl chlorid Chlorocarbon. See Carbon tetrachlorid ' ' Chlorocarbonic ether, ' ' 884 Chloro-ethane, 250. See also Ethyl chlorid Chloroform, administration of, 311-323 ammonia in, 287 apnea in, 298, 308 by drop method, 311 in case of acute mania, 669 in locomotor ataxia, 667 in passage of renal or biliary cal- culi, 667 Chloroform, administration of, in colonic ether anesthesia, 439 Snow's scientific, 23 with Braun 's inhaler, 323 with Gwathmey three-bottle vapor inhaler, 323 with Harcourt's inhaler, 320, 321 with Junker 's apparatus, 322 with Eoth-Drager oxygen and chloroform apparatus, 317-320 with the Yankauer mask, 203 alcohol as preservative of, 283, 285, 290, 291, 295 American, purity of, 891, 892 amount of, used with Eoth-Drager apparatus, 319 and shock, 389 as a solvent, 284 as preliminary to ether, 310 atropin as preliminary medicament to, 373 changes in, due to combination with oxygen, 294, 295 chemistry of, 281-297 Clover 's inhaler for, 23 combined with ethyl chlorid and ether (anesthol), 276-278 combining oxygen with, 80, 81 containers for, 292, 293, 294 the drop method, 200, 201 decomposition of, 289-296, 290, 883, 889 due to strong light, 295, 296 density of, 283 early prejudice against, 23, 25 early use of, 20-27 effect of agitation on, 296 effect of temperature on, 283 effect of warming on, 63, 64 effect of, upon blood pressure, 59 upon the circulatory system, 298- 302 upon the glandular system, 303-305 upon the kidneys, 303, 304, 309 upon the liver, 304 upon the muscular system, 302, 303 upon the nervous system, 302 upon the respiratory system, 298 elimination of, 309 ethyl chlorid and, 279 ethyl chlorid compared to, 258, 259, 260, 266, 267 experimental use of, in animals, 335, 336 fatty metamorphoses, following use of, 88 Harcourt's inhaler for, 26, 320, 321 history of, c.z an anesthetic, 281, 871- 873 impurities in, 285-289 fatal after-effects due to, 286-288 in A. C. E. mixture, 688, 689 in oil-ether rectal anesthesia, 462 in Schleich's mixture, 703-705 in spinal analgesia, 588 Moore-Eoaf theory of action of, 44, 45 906 INDEX Chloroform odor of, 889 organic impurities of, 890 Pilling dropper for, 312 preparation of, 285, 873-876 preservatives of, 290, 291, 292 pure, decomposition of, 289-296 purification of, 285, 877-883 relative anesthetic value of, 311 residue of, 889 safety of, 83 as affected by temperature, 314, 315 shipping of, 296 Simpson's early use of, 20, 21 Snow's inhaler for, 23 solubility of, 284 special physiology of, 297-310 specific gravity of, 283, 284, 889 stability of, 289 standards of purity for, 296, 297 substitutes for, 23, 24 temperature stimulus and, 69 uses of, in medicine, 284, 285 varieties of, of European make, 876, 877 verified tests for purity of, 889-891 warmed, 314 with acetic acid, 724 with air, safety of, 325 with alcohol, 295 with amyl nitrite, 698 with atropin, 371, 373 with chloral hydrate, 722 with ether, heat resulting from, 706- 710 in elderly persons, 328 in submucous operations, 340 nitrous oxid-ether sequence fol- lowed by, 325 statistics for, 842 with ethyl chlorid, 115, 116 dosage for, 116 rebreathing in the administration of, 115, 116 with morphin, 26, 371 with nitrous oxid and ether, 223, 224 Chloroform and oxygen, 26, 27, 87, 294, 295, 857 in adenoid and tonsil cases, 342 in brain operations, 354 in diabetes, 330 in dyspnea, 330 in elderly people, 328 in goiter, 353 in obese patients, 329 in obstetric cases, 355 in respiratory diseases, 330 in thyroidectomy, 353 in tuberculosis, 329 safety of, 325 statistics for, 843, 851, 855 Chloroform anesthesia, after-effects of, 310, 415 due to impurities, 286 antivom in, 712 blood changes due to, 58 Chloroform anesthesia, by intratracheal insufHation, 429 contraindications for, 310 kidney diseases, 330 rectal cases, 355 short operations, 338 status lymphaticus, 333 death due to, 305, 841, 842 excitement during, 307 for patients between 19 and 50, 328 in adenoid and tonsil cases, 341, 342, 343 ■ in cancer, 330 in children, 326, 327, 328 in circumcision, 355 in curettage, 355 in epileptics, 331 in heart diseases, 329 in insane patients, 331 in laparotomy, 355 in mastoid operations, 339 in obstetrics, 368 in operations for cleft palate, 340 in operations on the respiratory tract, 339 in peritonitis or intestinal obstruc- tion, 356 in sequestration anesthesia, 471 in submucous operations, 340 in tracheotomy, 353 indications for, 310 respiratory difficulties in, 380 stages of, 306-309 statistics for, 842, 843, 851, 852, 853, 854, 855, 857 status lymphaticus associated with, 331 use of Lewis pendulum swing in, 394-396 Chloroform Anschiitz, 877 Chloroform Liebreich, 876 Chloroform Pictet, 289, 877, 880, 881 Chloroform poisoning, 413 cases of, 414, 415 symptoms of, 415 use of oxygen and, 86 Chloroform Schering, 876 Chloroform treatment for acute pain in tetanus, 667 in cases of puerperal eclampsia, 667 in convulsive affections, 667 in strychnin poisoning, 667 "Chloroforme Officinal," 880 Chloroform-ether-chloroform sequence, 326 Chloroform-ether-menthol, 725 Chloroform-ether-nitrous oxid sequence, 141, 142, 143 Chloroform-ether-oxygen narcosis, 87, 88 Chloroform-ether sequence, 207, 208, 240, 326 statistics for, 843, 847, 848, 855, 857 Chloroforming, electric resuscitation following, 638-642 Chloroformium albuminatum. See Chloroformium Gelatinosum INDEX 907 Chloroformium colloidale. See Desal- gin Chloroformium gelatinosum, 725 Chloromethane. See Methyl Chlorid Chlorosis, sequestration anesthesia con- tra-indicated in, 470 * ' Chloroxycarbonic acid, ' ' formation of, on exposure of chloroform to light, 884 Chloryl, 725 anesthetic, 725 Cholecystectomy under spinal analgesia, 560 Christison, on action of sulphuric acid on chloroform, 878 Cinnamic acid as preservative of chloroform, 292 Cinnamon, tincture of, in dietetic shock, 387 Circulatory system, effect of anes- thetics on, 57-61 effect of ether upon, 185-188 effect of ethyl chlorid on, 259, 260 effect of nitrous oxid on, 128, 131 reflex changes in, in anesthesia, 61, 62 Circumcision, anesthesia in, 355 anesthetization of prepuce in, 514 ethyl chlorid anesthesia for, 268 separate injection of frenum in, 515 under complete spinal analgesia, 576 under local anesthesia, 486, 513, 514 under oil-ether colonic anesthesia, 464 Circumscribing injection in local anes- thesia, 495, 496 Citrate of potash in preliminary care ■ of kidneys, 364 Citronellol, as preservative of chloro- form, 292 Civil liability of physician, 681 Clark, on action of sulphuric acid on chloroform, 878 Clavicle, fractured, wiring of, under local anesthesia, 505, 506 Cleft kidney, associated with status lymphaticus, 333 Cleft palate, anesthesia in, 340 associated with status lymphaticua, 333 Climate and anesthesia, 853, 854 Closed method of administering ethyl chlorid, 273-276 of anesthesia, contra-indicated in elderly people, 328 in obese patients, 329 in status lymphaticus, 333 of etherization, Clover's, 177 ill effects of, on the lungs, 101, 102 Clover, J. T., 177, 749 on nitrous oxid and ether, 25 Clover chloroform inhaler, 23 Coburn apparatus for nitrous oxid- oxygen anesthesia, 149, 150, 151 Cocadrenal, 725 Cocasthylin 725 Cocain, 370, 483, 691, 692, 725, 726 and epinephrin, statistics for, 842 and ethyl chlorid, statistics for, 842 as preventive of cardiac inhibition, 402 discovery of, 555, 556 experimentation with, 555-559 in anesthesia of scalp, 497 in spinal analgesia, 576, 585, 600, 601, 604, 624 in tonsillectomy, 500 in treatment for sneezing, 387 in treatment of nose, 499, 500 injection of, preliminary to puncture in spinal analgesia, 618 introduction of, in local anesthesia, 478 poisonous action of, 478, 479 statistics for, 842 sterilization of, Bainbridge 's method of, 605 substitutes for, in local anesthesia, 478 toxicity of, 600, 601 use of, in dentistry, 538-543 precautions in, 539 preparation of solutions of, 539, 540 sterilization of solutions of, 540 substitutes for, 540-542 Cocain arabinate, 726 Cocain benzoate, 726 Cocain "block" in operations upon ex- tremities, 402 Cocain borate, 726 Cocain carbolate, 726 Cocain formate, 726 Cocain hydriodid, 726 Cocain hydrobromid, 726 Cocain hydrochlorid, 726 Cocain hydrochlorid solution with methaform, 773 Cocain infiltration, in general- anes- thesia, 485 in venous anesthesia, 491 Cocain lactate, 726 Cocain nitrate, 726 Cocain oleate, 726 Cocain phenate, 726 Cocain phenylate, 726, Cocain solutions, Bodine's tubes for, 482 Braun formulas for, 480, 481 for surface anesthesia, 489 preparation of, 479, 480 sterilization of, 480-482 syringes and bottles for, 48*1 Cocain spray, 727 Cocain tartrate, 727 Cocain-adrenalin anesthesia, operations under, 485 Cocain-adrenalin ointment, 726 Cocain-adrenalin solution for skin wheal production, 494 908 INDEX Cocain-adrenalin solution in anesthetiza- tion of urethra and bladder, 512 in circumcision, 513 Cocain-aluminum citrate, 726 Cocain-ethyl chlorid, 726 Cocainization of larynx for intra- tracheal insufflation, 427 Cocainol, 699, 727 Cocainol bismuth tablets, 727 Cocainol condurango tai)lets, 727 Cocainol quinin tablets, 727 Cocainol sanoform dusting powder, 727 Cocainolbalsam, Schmerzstillender, 727 Cocainol-creme, 727 Cocainol-Losungen, 728 Cocainol-menthol drops, 727 Cocainum arabinicum, 728 Cocainum phenylicum Merck-Oefele, 727 Cocainum phenylicum poinsot, 727 Cocainum phenylicum vian, 727 Cocain-urethane, 727 Co-capsulin, 728 Codrenin, 728 "Coin" freezing with ethyl chlorid, 670 Cold as local anesthetic, 477, 537, 728- 730 Cold perspiration in anesthesia, 60 Colic, biliary, anesthetic treatment in, 666 renal, anesthetic treatment in, 666 Collapse during anesthol administra- tion, 277 following ethyl chlorid anesthesia, 265, 272 Collins' technique in preliminary medi- cation, 372 Collodion, bottle for, 615 Colloidal chloroform, 732 Cologne, use of, in adenoid and tonsil operations, 342 Colombani on tropacocain in spinal analgesia, 601 Colon, distention of, in oil-ether colonic anesthesia, 462 Colonic absorption of ether, anesthesia by, 433-458 Color reflex in administration of chloro- form, 315, 316 Colton, G. Q., 10, 24 use of nitrous oxid in dentistry by, 118, 119 Combination and sequences in anes- thetics, list of, 325, 326 Combined oxygen narcosis, 87, 88 Comfort of patient during operation under local anesthesia, 486-488 "Compound anesthetic ether," 730 defined, 178 Compressed lozenges orthoform, 730 Compressed tablets anesthesin, 730 Compression of nerve trunks in local anesthesia, 476 Conductive anesthesia, 536 by perineural injection, 548-552 Conephrin, 730 Coniferin as preservative of chloro- form, 292 Conjunctival reflexes, absence of, in ethyl chlorid anesthesia, 263 in chloroform administration, 316 Connell on endopharyngeal anesthesia, 235, 238, 239 on ether vapor concentration, 241 Connell method of nitrous oxid-oxygen anesthesia, endopharyngeally, 159, 160 Connell 's anesthetometer, 160 Connell 's breathing tube, 392 Consciousness during spinal analgesia, 578 Contact anesthesia. See Pressure anes- thesia Containers for chloroform, 292, 293 for ether, 869 for ethyl chlorid, 254-256 glass vs. metal, 255, 256 Convulsions due to aromatic hydrocar- bons, 689 effect of warming the anesthetic on, 65 Convulsive affections, anesthetic treat- ment for, 667 Copper oxid in testing purity of oxy- gen, 895 Cordus, Valerius, ether prepared by, 858 Cork stoppers for chloroform contain- ers, objections to, 294 Corneal reflexes, absence of, in ethyl chlorid anesthesia, 263 Corning, discovery of spinal analgesia by, 556, 557, 558, 562, 563 on cocain, 478 sequestration method used by, 467, 468 Corona, 730, 731 Cortical neurons, effect of anesthesia on, 41 Coryl, 537. See also Chloryl Coryloform, 731 Coughing, during anesthesia, 381, 450 during intratracheal anesthesia, 429 Coughlin's ether rausch, 209-211 Cotton-Boothby apparatus for nitrous oxid - oxygen anesthesia, 160- 170 Cotton-Boothby introducing cannula, Ehrenf ried 's modification of, for soft rubber tubes, 426 Coumarin, 731 Craniotomy, bilateral suboccipital, in- tratracheal insufflation indicated in, 431 under colonic ether anesthesia, 454 under spinal analgesia, 587 Creme Dehne, 731 Creosote, 718, 731 Crile on anoci-association, 367-370, 388, 405, 463 on cerebrospinal fluid diffusion, 566 INDEX 909 Crile on combination of general with local anesthesia, 27, 485 on lumbar puncture, 558 on necessity of preliminary mental preparation, 366, 367, 369, 370 on prevention of shock, 385, 402-406 Crile method for gastro-enterostomy, 356 in goiter, 353, 354 of resuscitation, 642 Crile 's abdominal hysterectomy chart, 405 Crile 's case of death in nitrous oxid and oxygen anesthesia, 846 Crile 's chart of mortality rate of op- erations under anoci-association, 406 Crile 's pneumatic rubber suit, 404 Crile 's theory of de-oxygenation, as cause of shock, 401. See also Vasomotor paralysis Crile 's thyroidectomy chart, 406 Grim on medico-legal status of anes- thetist, 675-687 Criminal liability of physician, 685 Criminal negligence, 686 Criminals and resistance to surgical shock, 384 Crombil on medication before anesthe- sia, 26 on morphin and chloroform, 26 Cross and Spilsbury, on purity of chloroform, 882 Cuneo on ether disinfection, 673, 674 Cunningham, experiments of, on elec- tric resuscitation, 637 Cunningham apparatus for colonic ether anesthesia, 441, 444 Curettage, anesthesia for, 355 Cushing on local anesthesia, 493, 519 Cushing's anesthetization for inguinal hernia, 519-522 Cushing's sketch of nerves in inguinal hernia operations, 521 Custer, on use of sal anaesthicum Schleiehii, 809 Cyanosis, avoidance of, in nitrous oxid- oxygen anesthesia, 167 during intratracheal insufflation, 429 in asphyxia with ethyl chlorid, 261 in ethyl chlorid anesthesia, 263, 272, 275 in nitrous oxid anesthesia, 138, 134, 168 Cycloform, 731, 732 Cyclorenal, 732 Cyst, subcortical, removal of, under local anesthesia, 497 Cystitis, use of guaiasanol in, 763 Cystotomy, suprapubic, under local anesthesia, 513 Da Costa on Long, 8, 10 Dammersehlaf, 814 Dastre, statistics of, on chloroform anesthesia, 853 Davis apparatus for ethyl chlorid-ether by drop method, 223 for gas-ether by the drop niethod, 223 Davis dropper for insertion in original container, 206 Davis heater for gas or oxygen, 223 with the Gwathmey three-bottle vapor inhaler, 224 Davis inhaler for ethyl chlorid-ether sequence by the closed drop method, 222, 275 for gas-ether sequence, 221 Davis method of ether administration, 205, 206 of nitrous oxid anesthesia, 151 Davis nitrous oxid-oxygen apparatus, 145-148 Davy, Sir Humphry, on nitrous oxid, 4, 5, 118, 123 oxygen studied by, 893 Dawbarn's method of sequestration anesthesia, 468, 469 Death due to acidosis, 415 due to amylene, 698 due to chloral and ether, 722 due to ether, 415 due to lack of preliminary medica- tion, 370 due to shock, 384 in cases under anoci-association, 406 under chloroform anesthesia, 282, 287, 305, 414, 841, 842 under colonic ether anesthesia, 437, 455, 456 under ethyl chlorid anesthesia, 415 causes of, 261, 262 under intravenous anesthesia, 524 under spinal analgesia, 589, 596-598, 625 Debility, extreme, spinal analgesia in, 587 Decomposition of chloroform, 883-889 due to tin containers, 293 upon exposure to gas light or naked flames, 295, 296 Decomposition of pure chloroform, 289- 296 products of, 290 Deep breathing and concentration, 653 Deep sleep, hypnotic, 654 Defecation, involuntary, following use of nitrous oxid, 132 "Dehydrated ether," 197 Dehydration of protoplasm by anes- thetics, 34 Deimann, preparation of nitrous oxid gas by, 118 Delageniere 's method of sequestration anesthesia, 472 Delhaye on magnesium salts, 771 Denatured alcohol, methyl chlorid pro- duced from, 252, 253 Dental hypodermic needles, 543 Dental hypodermic syringe, 542 910 INDEX Dental operations under colonic etlier anesthesia, 435 Dental prop, use of, in ethyl chlorid anesthesia, 262 Dentalou, 732 Dentesthin, 732 Dentistry, chloroform contra-indicated in, 338- ethyl chlorid anesthesia in, 268, 338 local anesthesia in, by cocain, 538- 543 by cold, 537 by ethyl chlorid, 537, 538 by hypodermic method, 536, 537 history of, 535, 536 technique of injection, 543-553 nitrous oxid in, 118, 119, 338 nitrous oxid-oxygen anesthesia in, 173 Dentists as anesthetists, 676 Dentola, 732 Dentorol, 732 Deoxygenation as cause of shock, 401. See also Vasomotor paralysis of blood, an effect of chloroform, 299 Deoxygenation theory of anesthesia, 46 of nitrous oxid action, 124, 125 Dermatitis due to orthoform, 788 Desalgin, 732 Desguin on miagnesium sulphate, 771 Deutsches Arzneibuch, ethyl chlorid tests prescribed by, 257, 258 Dextrin in spinal analgesic solutions, 599 Dextrin-stovain solution for spinal analgesia, 603 Diabetes, acidosis in, 415 anesthesia in, 330 Diagnosis, use of anesthetics in, 667 Dialkylaminoalkyl, 3:4 — diaminobenzo- ates, 732 Diaphragm, effect of ethyl chlorid on, 258 effect of shock on, 385 position of, as it effects anesthesia, 59 Diarrhea following ethyl chlorid anes- thesia, 265 in cases under colonic ether anesthe- sia, 435, 436 Dichlorinated chlorid of methyl, 281. See also Chloroform Dichlormethane, 777. See also Methy- lene chlorid Dichloropropane, 733 Diet in acid intoxication, 413, 414 post-operative, 379 preliminary to anesthesia, 365, 366 Dietetic shock, 387 Diethyl ether, 178 Diethyl ketone, 804 Diethylaminaethyl benzoate, 733 Diffusion of cerebrospinal fluid, experi- ments on, 565-572 Digestive tract, effect of shock on, 385 Digitalin in spinal analgesia, 585 Dilatation of cardiac muscles due to chloroform, 300 of pupils in ethyl chlorid anesthesia, 261, 263, 274 Dimethyl ether, 776 . Dimethylacetal, 733 Dimethylcarbinol chloroform, 772 Dimethylketal, 689 Dimethylketone, 689. See also Acetone Dimethyloxyguinizin. See Antipyrin Dioform, 733 Dionin, 733, 734 o-Dioxyphenylethanolmethylamin, 830 Di-para-anisyl - monophenetyl - guanidin hydrochlorid. See Aeoin Dipropesin, 734 Displacement currents, production of anesthesia by, 629, 635, 636 Distribution coefficient and narcotic effect, 38, 39 Dizziness following use of ethyl chlorid, 338 Doleris on spinal analgesia, 560, 593 Dolonephran, 696, 734 Dolorant tablets, 734 Dolorifuge, 735 Donitz on spinal analgesia, 567, 568, 576 Dontocerat. See Ceratum odontalgi- cum Dott on action of sulphuric acid on chloroform, 878 on decomposition of chloroform, 887 on impurities in commercial acetone, 882 on preparation of chloroform from acetone, 874 Double-end ethyl chlorid tube, 254 Draeger 's pulmotor for artificial res- piration, 396-399 Drainage cases, care of, during anes- thesia, 375 Dreser on effect of ether vapor on the lungs, 101, 103, 105 on ether vapor concentration, 240 Drop method of chloroform administra- tion, 311-317 dropper for use in, 312 induction of anesthesia by, 312, 313 preparation of patient for, 312 reflexes in, 315, 316 warmed chloroform in, 314, 315 of ether administration, as antidote to drugs used in spinal anal- gesia, 598 in case of acute mania, 669 in locomotor ataxia, 667 in passage of renal or biliary cal- culi, 667 Dropper, ethyl chlorid, 256 Pilling chloroform, 312 Droppers for open method of ether administration, 199-202 Drowning, insufilation of pure air or air and oxygen in, 432 INDEX 911 Drowsiness, hypnotic, 654 Drug habitues, choice of anesthetic in, 329 ' ' Dry spine, ' ' effect of, on spinal anal- gesia, 585, 596, 621, 625 DuBois-Eeymond, on chloroform Pic- tet, 881 on imjiure chloroform, 288, 290 Dubois' theory of anesthesia, 34, 35 Dumas, formula of chloroform deter- mined by, 872, 873 Duration of operation and shock, 386 Dutch liquid, 749. See also Ethylene chlorid Dyspepsia, nervous, antivom in, 712 Dysphagin, 735 Dyspnea, anesthesia in, 330, 380 following overdose of nitrous oxid, 134 Ear operations, alypin in, 693 eucain lactate solution for, 758 under local anesthesia, 497-499 Edema of tissues by morphia-cocain in- jection, anesthesia by, 808 Edison's ansestheticum, 702 Ehrenfest's objections to spinal anal- gesia in obstetrics, 594 Ehrenfried's apparatus for intra- tracheal insufflation, 425, 426 Ehrenfried's introducing forceps for stiff or soft rubber tubes, 427 Einhorn, novocain discovered by, 482 Elayl chlorid. See Ethylene chlorid Electric analgesia, 735 application of, in man, 633-635 contra-indications to, 635 for surgical purposes, 634 history of, 628, 629 in wireless circuits, 635, 636 source of current for, 630 technique of, 630-633, 634 Electric current for dental anesthesia, 536 Electric resuscitation, 636, 637 after accidental electrocution, 642 application of, in surgery, 643 clinical application of, 643 exclusion of the head in, 637, 638 kind of current for, 638 limitations to, 641, 642 procedure for, 638-641 Electric sleep, contra-indications to, 635 distinguished from electric analgesia, 633 in wireless circuits, 635, 636 Electricity, anesthetic effect of, 51, 52 in local anesthesia, 477 Electrocution, electric resuscitation after, 637, 642 Electrodes, application of, for local electric analgesia, 634 Electrolysis, preparation of oxygen by, 894 Elimination of chloroform, 309 Elimination of ether, 107, 108 of ethyl chlorid, 263, 264 Elliottson, on hypnotic anesthesia, 644, 645 Elsberg, on anesthesia by intratracheal insufflation, 416-432 Elsberg 's apparatus for intratracheal insufflation, 419-423 Elsberg 's clip to hold intratracheal tube in place, 428 Embley, on ethyl chlorid, 258, 259, 260 on chloroform, 300, 302 Emergency cases, colonic ether anes- thesia contra-indicated for, 457 Emphysema, case of, following intra- tracheal insufflation, 430, 431 chloroform indicated for, 310 spinal analgesia in, 586 Empyema, anesthesia in, 329 under colonic ether anesthesia, 435 " Empyreumatic " oils in chloroform, 285 Endoneural injection in local anesthe- sia, 490 of the extremities, 506 Endopharyngeal administration of nitrous oxid and oxygen, 159, 160 Endopharyngeal anesthesia, 235-239 catheters for, 236 compared with endotracheal, 238, 239 essentials of, 237, 238 percentage of ether vapor for, 241 statistics for, 856 Endopharyngeal insufflation and mouth tube combined, 236 Endopharyngeal tubes for insufflation anesthesia, 227 Endotracheal anesthesia, compared with endopharyngeal, 238, 239 percentage of ether vapor for, 241 Endotracheal insufflation, in nitrous oxid-oxygen anesthesia, 173 statistics for, 855 See also Intratracheal insufflation Enema in preliminary treatment of in- testinal tract, 365 Engelhardt on after-effects of ether, 199 on effect of ether upon circulatory system, 185 "English chloroform," 876 English 's measures for shock preven- tion, 403 Engsted's method of spinal analgesia, 598 Enlarged tonsils, administration of nitrous oxid in, 140. See also Adenoid and tonsil cases Enophthalmin, 735 Ensemin, 735 Enteroepiplocele, umbilical, operation for, under spinal analgesia, 590 Enucleation, anesthesia in, 338, 339 Epicain, 735 912 INDEX Epigastric hernia under colonic ether anesthesia, 436 Epileptics, anesthesia in, 330, 331 chloroform indicated for, 310 electric analgesia contra-indicated in, 635 under spinal analgesia, 590, 591 Epinephrin, 691 injection of, preliminary to chloro- form anesthesia, 304 Epirenin borate in spinal analgesia, 602 Epsom salts, 735 Erhardt's solutions, 735 for spinal analgesia, 601 Erotic dreams in ethyl chlorid anes- thesia, 265 Erotic sensations during anesthesia, 687 Erythrophlein hydrochlorid, 735, 736 Esch, on action of adrenalin, 540 Esdaile, employment of hypnotic anes- thesia by, 645, 646 Esmarch bandage in local anesthesia, 477 in venous anesthesia, 490, 492 Esmarch inhaler, 204, 206, 217 Esophageal strictures under colonic ether anesthesia, 454 Essence of orange, 832 preliminary use of, 388 See also Oil of bitter orange peel Esters, defined, 178 Ethane, chlorination of, 252 ' ' Ethane-oxv-ethane, ' ' 178 Ethene, 736' Ethenyl-paradiethoxy-diphenyl - amidin hydrochlorid, 765 Ether, acidity of, 868, 869 action of hydrochloric acid on, 252 addition of, to ethyl chlorid and oxy- gen in alcoholics, 278 administration of. See Ether ad- ministration after-effects of, 199 American, purity of, 869, 870 and acapnia, 112 and alcohol, statistics for, 853 and amyl hydrid, 698 and chloroform in submucous opera- tions, 340 nitrous oxid-ether sequence fol- lowed by, 325 statistics for, 842, 853 use of, in elderly people, 328 and nitrous oxid, 141, 142, 143 statistics for, 842 and oxygen, 87 in cancer, 330 in heart disease, 329 in insane patients, 331 anesthetic, alcohol in, 181, 182 aldehyd in, 183 composition of, 179 peroxids in, 182 Ether, anesthetic, standards of purity to be maintained in, 181 average consumption of, in 100 cases under colonic anesthesia, 454 boiling point of, 864, 865 changes in, due to improper storage, 868 chemistry of, 178-184 chloroform-ether followed by, 326 colonic absorption of, 433-458. See also Ether administration combined with ethyl chlorid and chloroform (anesthol), 276-278 containers for, 182 early experimenters with, 11-19, 434 effect of, on blood pressure, 59 on the circulatory system, 185-188 on the glandular system, 189 on the muscular system, 189 on the nervous system, 188 on the respiratory system, 185 effect of warming on, 66 ethyl chlorid and, 279 ethyl chlorid compared to, 266, 267 Faraday's use of, 5 fatty metamorphoses following use of, 88 first use of, in midwifery, 20, 177 from ethylene, 862 from "methylated" alcohol, 861 history of use of, as an anesthetic, 176-178, 858-860 hypnotism and, 645 impurities in, administration means to avoid, 183-184 sources of, 179 in A. C. E. mixture, 688, 689 in acid intoxication, 414 in cases of puerperal eclampsia, 667 in chloroform, 284, 285, 307 in cocain sterilization, 605 in convulsive affections, 667 in intravenous anesthesia, 525, 530, 532, 533 in Schleich's mixtures, 703, 704, 705 in sterilization of apparatus for spinal analgesia, 616 in strychnin poisoning, 667 in treatment of acute pain in tetanus, 667 in treatment of infections, 671-674 eases of, 672, 673 Long's use of, 8-10 manufacture of, 180, 860-863 Morton's experiments with, 11, 12 nitrous oxid-ether sequence followed by, 325 peroxids in, experiments of Basker- ville and Hamor on, 182-183 Pierson's use of, 4 precautions in handling, 179 purity of, 864-870 respiratory failure due to, 192 role of water in, 867, 868 special physiology of, 184 specific gravity of, 864, 867, 868 INDEX 913 Ether, temperature stimulus and, 69 tests for purity of, 864-867 use of oil of bitter orange peel with, 93, 94 varieties of, in Great Britain, 861 warm, nitrous oxid and oxygen com- bined with, 325 with air, safety of, 325 with nitrous oxid and chloroform, 223, 224 with nitrous oxid and morphin, 108 with oxygen, safety of, 325 See also Ethyl ether Ether administration, 100-103, 199-247 Allis inhaler for, 216 Bennett inhaler for, 218 by colonic absorption, 433-458 advantages of, 457 afferent and efferent tube systems in, 449, 450 apparatus for, 437, 438, 441, 442, 444-449 cases of, 435-437, 453-458 complications in, 435, 436 danger signs in, 453 development of, 441-444 history of, 433-439 indications and contraindications for, 457, 458 method for, 441-444; 450-453 physiology of, 439-441 Sutton's method of, 441, 444, 448 by intratracheal insufflation, 416-432 causes of death from, 192 closed method of, 177, 217 Esmarch inhaler for, 217 handkerchief method of, 212-217 open or drop method of, 198, 199 as antidote to drugs used in spinal analgesia, 598 Davis's, 205, 206 droppers for, 199-202 in case of acute mania, 669 in locomotor ataxia, 667 in passage of renal or biliary cal- culi, 667 masks for, 202-204 Mayo's, 203-205 percentages of vapor for, 241-244 rebreathing in, 100-115 semi-closed method of, 211 Snow 's inhaler for, 23 with closed masks, ill effects of, 101, 102 with nitrous oxid, 218 with oxygen, 239, 240 with the ether rausch, 209-211 with warm water — vapor inhalations, 199 Ether anesthesia, after-effects of, 196- 199 blood changes due to, 58 cone method of, 198 contraindications to, 328 brain operations, 354 Ether anesthesia, diseases of respiratory passages, 330 kidney diseases, 330 short operations, 338 tuberculosis, 329 danger of shock with, 388 death due to, 841 discovery of, 7 excitement stage of, 193 exhaustion under, 405 first operation in England under, 19, 177 in adenoid and tonsil cases, 340, 341, 342 in children, 327 in England, 19 in epileptics, 331 in Graves' disease, 353 in mastoid operations, 339 in obstetrical cases, 355 in operations for cleft palate, 340 in operations on the respiratory tract, 339 in peritonitis or intestinal obstruc- tion, 356 in sequestration anesthesia, 471 in status lymphaticus, 333 indications and contra-indications of, 247-249 indications of returning conscious- ness under, 195 light stage of, 193 normal surgical stage of, 194 overdose stage of, 195 statistics for, 842, 843, 848, 853, 854, 855, 857 Ether balance, maintenance of, in re- breathing, 106 Ether-chloroform-ether sequence, 326 Ether-chloroform-oxygen narcosis, 87, 88 Ether-chloroform sequence, 326 drop method of, Lumbard's nasal tubes for, 229 for elderly patients, 234 heat resulting from, 706-710 statistics for, 843, 855 Ether cMorohydrique, 250. See also Ethyl chlorid Ether concentration in colonic anesthe- sia, 441 Ether controversy between Morton, Jackson and Wells, 17, 18, 19 Ether elimination, 107, 196, 379 effect of morphin on, 108 Ether frolics, 7, 9, 177 Ether irrigation of the abdomen, 672- 674 Ether-menthol-chloroform, 736 Ether, morphin and scopolamin, statis- tics for, 842 Ether poisoning, delayed, 440 Ether pressure, 242-244 Ether rausch, Coughlin on, 209-211 Ether spray in dentistry, 537 invention of, as local anesthetic, 477 914 INDEX Ether storage, impurities developed in, 180 "Ether-tremor," 194 Ether vapor, administration of, by Meltzer's method, 238 advantages of, 246 by open method, 231-235 concentration of, 240 effect of, on respiratory passages, 101-103 in adenoid and tonsil eases, 340, 343 in tracheotomy, 353 mask for, 232 maximum concentration of, without irritation, 103, 105, 106 Pinneo's apparatus for, 234, 236 treatment of accidents under, 246, 247 use of, with nitrous oxid and oxy- gen, 164, 165, 167, 168, 172 warmed, 25, 225-227 experiments with, 70-76 Gwathmey 's administration of, 231 temperature required for, 227, 228 Etherization, open and closed methods of, compared as to toxic effects, 102 Ethical liability of physician, 680, 681 Ethidene bichlorid, 750 Ethidene dichlorid. See Ethylidene chlorid Ethyl acetate, 736 in chloroform, 285 Ethyl alcohol, 737 in. chloroform, 283, 289 in drop method of ether administra- tion, 182 in manufacture of ether, 180, 181, 182 preparation of chloroform from, 873 preparation of ethyl chlorid from, 252 presence of, in chloroform, 891 Ethyl aminobenzoate, 737, 738 statistics for, 843, 856 Ethyl bromid, 692, 738-748, 750 combined with methyl chlorid and ethyl chlorid (somnoform), 276 dosage for, 739 Ethyl carbamate, 838 Ethyl chlorid, 20, 27, 691, 692, 748 after-effects of, 264, 265 and air, 276, 325 and chloroform, 115, 116, 279, 285 rebreathing in administration of, 115, 116 statistics for, 842 and ether, 279 statistics for, 842, 848, 855 and nitrous oxid, 279 and oxygen, 278, 279, 325 statistics for, 843, 856 atropin as preliminary medicament to, 373 bottle for, 615 Ethyl chlorid, causes of death under, 261 chemical history of, 250, 251 combinations and sequences with, 276-279 comparison of, with other anesthetics, 266, 267 containers for, 254-256 contra-indications to, 268, 269, 338 danger of shock with, 388 dosage of, 269-271 effect of, on blood pressure, 59 on circulatory system, 259, 260 on glandular system, 261 on muscular system, 261 on nervous system, 260, 261 on respiratory system, 258, 259 effect of warming on, 66 elimination of, 263, 264 experimental data on administration of, 269-271 for anesthetizing children, 327 for local anesthesia in dentistry, 537, 538 history of use of, as an anesthetic, 251 impurities in, 252, 253, 257 detection of, 257, 258 in convulsions of infancy and child- hood, 667 in Meyer's anesthol, 704, 705 indications for, 267, 268 introduction of, into England, 27 methods of administration of, 271, 272 closed, 273-276 open, 272 semi-closed, 272, 273 nitrous oxid with oxygen combined with, 325 preliminary to puncture in spinal analgesia, 618, 620 preparation of, 251-253 properties of, 253, 254 purification of, 253 solubility of, in water and in blood serum, 259 stages of anesthesia with, 261-263 statistics for, 842, 843, 848-850, 855, 857 storage of, 254-256 therapeutic uses of, 670, 671 uses of, 251 Ethyl chlorid-anesthol, statistics for, 843, 856 Ethyl chlorid bengue, 748 Ethyl chlorid C. P., 748 Ethyl ehlorid-ether-ehloroform se- quence, 206, 325 Ethyl ehlorid-ether sequence, 325 by closed method, 207 by drop method, 206 for patients between 19 and 50, 328 statistics for, 843 Ethyl chlorid measure dropper, 256 Ethyl chlorid polychlorated, 748 INDEX 915 Ethyl ehlorid spray in local anesthesia, 477 Ethyl ehlorid syncope, 261 Ethyl ehlorid toxemia, 261 Ethyl ehlorid tubes, 254-256 Ethyl ether, 178, 748 as preservative of chloroform, 292 discovery of, as an anesthetic, 7 Ethyl ether-chloroform mixtures, 748 Ethyl formate, 748 Ethyl hydrid, 748 Ethyl iodid, 748 action of chlorin on, 252 Ethyl-morphin hydrochlorid, 733 Ethyl-6-anisidin formate, 749 Ethyl nitrate, 749 Ethyl nitrite, 749 Ethylbenzoylecgonin, 725, 738 Ethylen 689 Ethylene, ether from, 862 Ethylene ehlorid, 749 in chloroform, 285 Ethylene dibromid, 750 Ethylene (monochloro-) ehlorid, 750 Ethylic ether, 178 Ethylidene dimethyl ether, 733 Ethylidene ehlorid, 750 in chloroform, 285 introduced by Clover, 25 Ethylol, 250, 751. See also Ethyl ehlorid Ethylpropionyl, 804 Ethylurethane, 838 Eucain in local anesthesia, 478 in spinal analgesia, 599 statistics for, 842 Eucain-A, 751-754 Eucain acetate, 756, 757 Eucain-B, 540, 752 in local anesthesia, 482 Eucain lactate, 757, 758 Eucain-snuff powder, 758 Eucalyptus extract, 758 Eucapren, 758 Euearenalin, 758 Eudont, 758 Eudrenin, 758, 759 Eugallol, 759 Eugenic acid. See Eugenol. Eugenol, 759 Eugenol acetamid, 759 Eugenol-alcohol, 759 Eugenol esters of the aminobenzoic acids, 759 Euphorin, 802, 803. See Phenyl-ure- thane Euprema, 760 Euroform paste, 760 Euscopol, 760 Eusemin, 760 Evans, and nitrous oxid, 24 Excitement preceding narcosis, 33 Excitement stage, effect of oil of bitter orange peel on, 93, 94, 95 in ethyl ehlorid anesthesia, 262 In nitrous oxid anesthesia, 133 Exophthalmic goiter, in status lym- phaticus, 332, 335 preliminary medication in, 372, 373 Exophthalmos, anesthesia in, 353, 354 Experimentation, animal, with oil- ether colonic anesthesia, 458-460 Extralaryngeal operations under co- lonic ether anesthesia, 435 Extremities, operations on, eocain "block" in, 402 intravenous anesthesia for, 492, 506, 509, 511 under local anesthesia, 490, 506- 512 Extremities, lower, operations on, under spinal analgesia, 586, 588, 597, 610 upper, nerve distribution of, 508 superior, operations on, under spinal analgesia, 597 Eye, effect of eucain-A on, 751 enucleation of, under colonic ether anesthesia, 454 use of nervocidin in, 781 Eye surgery, eucain lactate in, 758 under colonic ether anesthesia, 454 under local anesthesia, 500, 501 Eyeballs, in ethyl ehlorid anesthesia, 263, 274 Eyelid, operations on, under local anes- thesia, 497 separation of, in overdose of ethyl ehlorid, 261 Fabre on the effect of ether on lacta- tion, 192 Face, changes in, due to shock, 385 nerve supply of, 497 Face mask, Teter, for nitrous oxid-oxy- gen anesthesia, 154 Facial operations, chloroform indicated for, 310 under local anesthesia, 497, 498 Fainting, following ethyl ehlorid anes- thesia, 265 Faivre on spinal analgesia, 564 Falkenstein 's zahnpasta, 760 False chloroform anesthesia, 380 Faraday on ether, 5, 177 Farina cologne in chloroform adminis- tration, 312, 316 Fatty degeneration of kidneys and liver, following repeated admin- istrations of ethyl ehlorid, 265 Fatty metamorphosis and anesthesia, 88, 90 Favill on acid intoxication due to anes- thetics, 414 Fear, diagnostic evidences of, 368, 369 prevention of, 388 prior to anesthesia, effect of, 366, 369, 370 Fedorow on intravenous anesthesia, 524 Ferguson 's artificial airway, 39 1 Ferguson's ethyl ehlorid tubes for gen- eral and local anesthesia, 255 916 INDEX Ferguson's mask for ether administra- tion, 203, 204 Fetus, effect of ether upon the, 191 Fever after spinal analgesia with tropo- cocain, 583 Fevers, infectious, acidosis in, 415 Field, Justice, legal status of physician determined by, 678, 679 Filliatre on cocain in spinal analgesia, 600 Filodentol BertagnoUi, 760 Finger, cross-section of, 509 Finger anesthetization, 507 Finger operations, 354 Esmarch elastic bandage in, 477 Finnemore and Wade on alcohol pre- pared from ethyl alcohol, 882 Fischer's apparatus for intratracheal insufflation, 423, 425 Fischer's "normal anesthetic solu- tion," 541 Fisher on paralyses after spinal anal- gesia, 584 Fistula in ano, colonic ether anesthesia contra-indicated in case of, 457 Flexible spraying nozzle for ethyl chlorid, 254 Flushing of face associated with ethyl chlorid anesthesia, 260 Foot, removal of tuberculous abscesses of, under spinal analgesia, 575, 576 Foramen ovale, section through, 500 Forbes, Sir John, on hypnotic anes- thesia, 644 Forearm, cross-section of, 507 Forel's classification of hypnosis, 654 Forel's method of inducing hypnosis, 658 Formal, 776, 777. See also Methylal Formaldehyd, 689 in testing chloroform for impurities, 890 Formaldehyd-kelene, 760 Formanilid, 760 Formic acid, formation of, on expos- ure of chloroform to light, 884 in chloroform, 285, 286 Formic ether, 748 Formyl tribromid. See Bromoform Formyl trichlorid, 281. See also Chloroform Fortescue-Brickdale, on methyl ether, 776 Foureroy on ether, 860 Foy, George, on chloroform, 26 Fractures, treatment of, under colonic ether anesthesia, 454 under infiltration of cocain and adrenalin, 508, 509 under intravenous anesthesia, 492 Fraicon's auto-operation under spinal analgesia, 577 Fraicon's solution for spinal analgesia, 577 Francis, on methyl ether, 776 Freezing as a means of local anesthe- sia, 537 in anesthetization of skin, 493 with anaesthyl, 710 with ethyl chlorid as local anesthetic, 477, 670 French on sequestration with upright position, 473-475 on use of oil of bitter orange peel, 94 French chair table, 346-351 French Codex, ethyl chlorid tests pre- scribed by, 258 French method of adenoid and tonsil operations in upright position, 345-352 Fresenius ansesthesin-bormelin. See Anaesthesin-bormelin Frink, H. W., on hypnosis, 653-665 Frink 's method of inducing hypnosis, 658-664 Fritsche's method of preparing ether from ethylene, 862 Frobenius, experiments of, with ether, 859, 860 Frohmann's solution, 760 Furfurane, 714 Furniss gas-ether inhaler, 220 Gajacyl. See Guaiacyl Gall-bladder operations, shock in, 403 under local anesthesia, 518, 519 Gallotannic acid as preservative of chloroform, 292 Ganglia, sympathetic, excision of, un- der spinal analgesia, 587 Ganglion cells, effect of ethyl chlorid on, 260 in anesthesia, 34, 36, 37 role of, in ethyl chlorid anesthesia, 264 Gangrene from Esmarch elastic band- age, 477 of intestine, operation for, under spinal analgesia, 593 senile, spinal analgesia in, 587 Gas-ether-chloroform sequence, 326 in adenoid and tonsil cases, 342 Gas-ether sequence, 326 contra-indicated in elderly people, 328 for patients between 19 and 50, 328 in adenoid and tonsil cases, 342, 343 in nervous patients, 330 Gasoline, 761. See also Pentane Gasserian ganglion, cannula insertion for, according to Haertel, 501 injection of, in local anesthesia, 498 removal of, under colonic ether anes- thesia, 454 Gasserian ganglion puncture according to Haertel, 498 skin wheal for, 500 Gastralgia, ethyl aminobenzoate in, 737 Gastric ulcer, acidosis in, 415 antemesin in, 711 INDEX 917 Gastric ulcer, use of orthoform-new in, 789 Gastro-enterostomy, anesthesia in, 356 hypodermoclysis in, 376 under local anesthesia, 518 Gasu-basu. See Nervocidin Gatch, W. D., on rebreathing in ad- ministration of anesthetics, 27, 100-116 Gatch 's method of administering ni- trous oxid and oxygen, 144-151 Gatch 's nitrous oxid-oxygen apparatus, 104 "Gauze ether" method, 102 Gebauer container for ethyl chlorid, 256 Gebauer tube for administration of ethyl chlorid in dental anesthe- sia, 537 General anesthesia, theories of, Baglioni's, 46 Bernard's, 34 Binz's, 34 Barker's, 48 Dubois', 34, 35 Gill's, 46 Gros's, 48 Hober's, 46 Lillie's, 50-55 Mathews-Brown, 42-44 Meyer-Overton, 37-40 Moore-Eoaf, 44-46 MuUer's, 36, 37 Eeicher's, 47, 48 Schleich's, 35, 36 . Spencer's, 32-34 Traube's, 42 Verworn's, 49, 50 Wright's, 40-42 General anesthetics, chief, 32 definition of, 31 requirements of, 31, 32 Genitals, external, site of spinal punc- ture for operations on, 610 Genito-urinary diseases, sanovagin in, 727 Genito-urinary operations, anesthesia in, 355 under local anesthesia, 512, 513 under spinal analgesia, 560, 587 Geraniol, as preservative of chloroform, 292 German chloroforms, 876, 877 Gerstenberg on spinal analgesia, 564, 621 Gessner, Conrad, 858 Geuther, preparation of chloroform from carbon tetrachlorid by, 875 Gibbs' method of purifying chloro- form, 879 Giesel, discovery of tropacocain by, 832 Gill on chloroform, 297, 299, 305 Gill's theory of anesthesia, 46 Giswold on use of quinin and urea hy- drochlorid, 806 Glacial, 761 Gland removal from neck under spinal analgesia, 587 Glands, enlarged, chloroform indicated for, 310 Glandular system, effect of anesthetics on, 60, 61 effect of /Jhloroform on, 303-305 effect of ether on, 189 effect of ethyl chlorid on, 261 effect of nitrous oxid on, 131, 132 Glass containers for ethyl chlorid, 255, 256 Gleditschin. See Stenocarpin Glottis, closure of, by the tongue, 390 Glucose in dietetic shock, 387 in spinal analgesic solutions, 599, 602, 603 use of, preceding anesthesia in can- cer, 330 Glucose-adrenalin-stovain solution in spinal analgesia, 625 Glycogen, importance of, in liver, dur- ing anesthesia, 365, 366 Glycosuria in ether narcosis, 191, 196- 198 Goiter, anesthesia in, 353, 354 operations for under colonic ether anesthesia, 454 under local anesthesia, 502-505 under spinal analgesia, 580 sequestration anesthesia indicated in, 469 Goldan on spinal analgesia, 567 Goldschmidt 's anaesthetics, 761 Goldstein, experiments of, with nitrous oxid, 126, 127 Goyanes on arterial injection, 478, 492 Graham's theory of etherification, 863 Graves' disease, anesthesia in, 353, 354 use of scopolamin contra-indicated in, 815 Gray on eucain-B, 755 on spinal analgesia, 587, 588, 589, 590, 598 dextrin-stovain solution by, 603 site for spinal puncture by, 610 Gray's auEestheticum, 702, 761 Grayson's statistics for chloroform, 852 Gregory, on chloroform prepared from ethyl alcohol, 882 Gregory's method of purifying chloro- form. 878, 879 Grehant's anesthetic, 761 Groin, diffuse mfiltratiou in, 510 removal of glands of, under local anesthesia, 485 Grondahl on effect of ether on the kid- neys, 189 Gros, conclusions of, on relation of gen- eral and local anesthetics, 48 on novocain bicarbonate solutions, 786 Gross ignorance or negligence, on part of physician, 685, 686 Groves, J. F., on Long, 8 918 INDEX Grube on effect of ether upon body temperature and carbohydrate metabolism, 197 on glycosuria in ether narcosis, 191 Guaiacol, 761, 762 as preservative of chloroform, 292 Guaiacyl, 762 Guaiasanol, 762 Guajacid, 762 Gujasanal. See Guaiasanol Gum acacia, addition of, to tropaco- cain, 837 Gum arable in spinal analgesic solu- tions, 599, 601 Gummitropakokain, 763 Gums, operations on, under local anes- thesia, 497 Guthrie, discovery of chloroform by, 871, 872 Guthrie and Eyan on magnesium salts, 771 Gwathmey, anesthetization of a case of acute mania by, 668-630 experiments of, on warming anes- thetic agents, 63-66, 69 with oxygen combined with anes- thetic agent, 82-86 use of oil of bitter orange peel by, 92, 93 Gwathmey inhaler, for nitrous oxid- ether sequence, 218, 219, 220 Gwathmey method of nitrous oxid-oxy- gen anesthesia, 153 Gwathmey nitrous oxid-oxygen appar- atus, 150 Gwathmey oxygen Y-piece, 151 Gwathmey rectal irrigating tube, 461 Gwathmey three-bottle vapor inhaler, 317, 323, 334 Gwathmey vapor apparatus, 71, 72 Gwathmey vapor inhaler, 147, 148 Gwathmey and Alexander on adenoid and tonsil cases, 340-352 Gwathmey and Baskerville, experiments of, on warming ether vapor, 71- 73 Gwathmey-Woolsey mask for nitrous oxid-oxygen anesthesia, 172 Gwathmey-Woolsey nitrous oxid-oxygen apparatus, 170-175 Gynecology, ethyl chlorid anesthesia in, .268 local anesthesia in, 516 use of scopolamin in, 813, 814 use of tropacocain in, 836 Haertel's method of nerve blocking, 498 of reaching Gasserian ganglion, 501 Hager on effect of light on chloroform, 884 on "English chloroform," 876 Halbreich's experiments on cerebro- spinal fluid diffusion, 566 Hallucinations, due to nitrous oxid, 131 Hallux valgus, injection of skin in- cision for, 510, 511 Hamblen on acetonuria after ether, 198 Hamor and Baskerville, on decomposi- tion of chloroform, 887-889 Handkerchief method of ether adminis- tration, 212-215 Harcourt's inhaler, 26, 320, 321 Harley, "A. C. E. .mixture" by, 23 on spinal analgesia, 556 "Hashish," 3 Hassler, J. Wyllis, on intravenous anes- thesia, 523-534 Hatcher, on scopolamin, 815 Hawk on effects of ether on the urine, 197 on glycosuria after ether, 196 Hay fever, formaldehyd-kelene in treat- ment of, 760 rhinosol for, 808 use of orthoform-new in, 789 Hayden on surgery under anesthesia, 14-16 Hay ward on Bier, 492 on chloroform, 25 Head, exclusion of, in electric circuit for resuscitation, 637, 638 operations on, colonic ether indicated in, 457 intratracheal insufflation indicated in, 431 under local anesthesia, 496-501 under spinal analgesia, 597 Head and neck cases under colonic ether anesthesia, 436 Headache after spinal analgesia, 583 following ethyl chlorid anesthesia, 264, 265 Healing after local anesthesia, 488 Heart, action of chloroform upon, 299, 301, 317 concomitant affections of, spinal analgesia contra-indicated in, 587 effect of anesthetics on, 59 effect of ethyl chlorid on, 258, 259, 260 effect of nitrous oxid on, 130 effect of nitrous oxid and oxygen on, 670 effect of shock on, 385 effect of warming the anesthetic on, 65 Heart disease, choice of anesthetic in, 328, 329 Heart failure, death due to, in status lymphaticus, 333 Heart lesions, colonic ether anesthesia indicated in, 457 Heat during colonic ether anesthesia, 458 effect of, on ethyl chlorid, 253 from ether and chloroform combina- tion, 705-710 moist, as preventive of shock, 402 INDEX 919 Heat. See also Warming the anes- thetic agent ' ' Heavy oil of wine, ' ' 864 Hedonal, 763, 764 in intravenous anesthesia, 532, 533 Hein on spinal analgesia, 564, 621 Helleborein, 764 Hellman, on training of anesthetists, 676 Hemoglobin, role of, in anesthesia, 44, 45 Hemorrhage, control of, by sequestra- tion anesthesia, 468, 470, 473- 475 during anesthesia, saline enema for, 376 with colonic ether, 436, 455, 456 post-operative, in local anesthesia, 483 Hemorrhoids, operations for, under local anesthesia, 485 use of suppositoires adreno-styp- tiques in, 830 Hemostatic cocainol bougies, 727 Henderson, 101, 388, 406 on acapnia as cause of shock, 401. on acapnia in rebreathing, 112 on arterial pressure due to shock, 408 on death due to ether, 192 on physiological role of carbon di- oxid, 97, 98 on vasomotor hyperactivity as cause of shock, 406-409 use of magnesium chlorid by, 771 Hennell, observations of, on etherifica- tion, 862 Henry VIII, medical profession estab- lished under, 678 Hernia, abdominal, operation for, un- der oil-ether colonic anesthesia, 464 femoral, operation for, under local anesthesia, 522 inguinal, cure of, under local anes- thesia, 519-523 operation for, under spinal anal- gesia, 579, 580, 588, 591, 625, 626 post-operative ventral, operation for, under local anesthesia, 523 recurrent, operation for, under local anesthesia, 522 umbilical, operation for, under local anesthesia, 522, 523 scheme of injection in, 522 Hernia incision, relation of inguino- scrotal nerves to, 520 Hernia operations, ether disinfection in, 672, 673 under colonic ether anesthesia, 441 under local anesthesia, 485, 486, 490, 519, 521 under spinal analgesia, 577, 625 Herrenknecht, 267 on ethyl chlorid anesthesia, 262, 263 Hertel's solution for spinal analgesia, 601 Hertzler on urea and quinin hydro- chlorid as local anesthetic, 483, 500, 515 Hervey on warmed ether vapor, 229- 231 Heufiber-renitol, 764 Heufibrol-cr^me Stauffer, 764 Hewitt, Frederick D., 3, 8, 832 on administration of nitrous oxid with air, 141 on causes of death under ethyl chlorid anesthesia, 261 on combining oxygen with anesthetic agent, 80, 81 on effects of chloroform, 285, 305, 667 on ethyl chlorid anesthesia, 267, 271 on methylated ether, 861, 862 on nitrous oxid and oxygen, 25 on nitrous oxid-ether-chloroform, 852 on oxygen-ether administration, 239 on respiratory failure due to ether, 192, 193 statistics of, for ether and for chloroform, 852-854 Hewitt's artificial airway, 390, 391 Hewitt's breathing tube in intravenous anesthesia, 530 Hewitt's C. E. mixture, 764 Hewitt's method, of administering ethyl chlorid, 275, 276 of nitrous oxid-oxygen anesthesia, 151-153, 161 Hewitt-Mason's mouth-gag with anes- thetic tubes, 322 Hexachlor-benzene in chloroform decom- position, 295 Hexachlorethane in chloroform, 285 Hexahydrophenanthrene, 764 Hexamekol, 764, 765 Hexane, 765 Hiccough during anesthesia, 381 Hickman, Henry Hill, 5-7, 719 High arterial pressure, electric anal- gesia contra-indicated in, 635 History of anesthesia, 1-29 H. M. C, ether and, statistics for, 856 Hober's theory of anesthesia, 46 Hoffmann, on temperature in ether- drop-anesthesia, 69 preparation of ether by, 859 Hoffman 'sche Tropfen, 859 Hohmeier, on death due to spinal anal- gesia, 598 Holocain and adrenalin ointment, 765 Holocain hydrochlorid, 765 hydrochlorid in spinal analgesia, 563, 599 Holscher on effect of ether vapor on the lungs, 102 Homatropin, 688 Homeopathy and allopathy, 678 Honan, William F., on intravenous anesthesia, 523-534 920 INDEX Hooker's tracing showing effect of weak ether vapor on pyloric ring of frog, 114 Hoseman on lumbar pressure, 583 Houghton on spinal analgesia with Barker solution, 602 Humphrey's "Medicated Vapors," 7 Hutchinson, anesthetic properties of induction currents discovered by, 628 Hyderabad Chloroform Commission, 26 Hyderabad Commission, on cardiac in- hibition, 302 Hydramyl, 697, 767 Hydramyl ether, 767 Hydramyle, 767, 768 ''Hydrate of ether," 178 "Hydrate of ethylene," 178 Hydriodic ether, 748. See also Ethyl iodid Hydrobromic ether, 738-748. See also Ethyl bromid Hydrocele under colonic ether anes- thesia, 454 under oil-ether colonic anesthesia, 464 Hydrochloric acid in chloroform, 285, 286, 293, 294 in chloroform decomposition, 296, 883-888 in preparation of ethyl chlorid, 252 test for, in ethyl chlorid, 257 Hydrochloric ether, 250. See also Ethyl chlorid Hydrogen, discovery of, 4 Hydrogen chlorid as product of pure chloroform decomposition, 290 in preparation of ethyl chlorid, 252 Hydrogen dioxid, 364 in chloroform, 286 in disinfection of mouth, 364 Hygienic treatment preliminary to anesthesia, 364-366 Hyndham and Mitchener on magnesium sulphate, 771 Hyoscin in post-operative treatment, 378 in preliminary medication, 371 for spinal analgesia, 612 Hyoscin hydrobromid in preliminary medication for oil-ether colonic anesthesia, 461. See also Sco- polamin hydrobromid Hyoscin-morphin-cactin combination, 372, 768. See also H. M. C. Hyoscin-morphin mixture, 768 Hypercapnia in rebreathing. 111 Hyperoxygenation theory of nitrous oxid action, 123, 124 Hyperpnea following overdose of ni- trous oxid, 134 in anesthesia, 380, 389 Hypersensitiveness to anesthetics, 832 Hypertension, sequestration anesthesia contra-indicated in, 470 Hyperthermia after spinal analgesia, 582 Hyperthyroidism, 354 Hypnosis, different degrees of, 654, 655 induction of anesthesia under, 664, 665 methods of inducing, 657-664 Hypnotism, 2, 644-653 advantages of, in anesthesia, 647 anesthesia by, 644-646 attitude of the hypnotist in, 656, 657 charlatanism and, 649 chemical anesthetics and, 645-647 disadvantages of, 648, 649 early history of, 4 factors influencing, 655, 656 in childbirth, 647, 648 in minor operations, 648 Hypochlorites, preparation of oxygen from, 894 Hypodermic apparatus, 484 for dental use, 542, 543 Hypodermic injection in shock preven- tion, 403 prior to local anesthesia, 486 Hypodermic method of local anesthesia in dentistry, requirements for, 536, 537 Hypodermic syringe, invention of, 478 Hypodermoclysis in gastro-enterostomy, 356, 376 in treatment for shock, 374 Hypophosphorous acid as preservative of chloroform, 292 Hypotaxis, 654 Hysterectomy, abdominal, under anoci- association, 405 under spinal analgesia, 560 Hysteria, control of, 374 use of hedonal in, 764 Hysterical symptoms following ethyl chlorid anesthesia, 265 Ice and salt, 768 Ice packs for painless dentistry, 537 Ichnol, 768 Icterus, post-operative, following se- questration anesthesia, 472 von Idelson on chloroform and oxygen, 27 Idin, 768 Idiosyncrasy and failure to produce spinal analgesia, 585, 623, 624 Idiosyncratic difficulties during anes- thesia, 832 Idiots, psychic treatment for, prelim- inary to anesthesia, 366 Illegal operations, law relating to anesthesia in, 687 Incision through skin and platysma muscle in goiter operation, 504 Incisive fossa, location of, 551 Induction currents, production of anes- thesia by, 628, 629 INDEX 921 Infants, selection of anesthetic for, 326 Infections, ether treatment of, 671, 672 Inferior maxilla operations under co- Ionic ether anesthesia, 454 Infiltration in anesthesia of the ex- tremities, 506, 508, 509 in anesthetization of skin, 493 in excision of varices, 511 in external urethrotomy, 512 in eyelid operations, 497 in facial operations, 497 in gynecology, 516 in hernia anesthetization, 522, 523 in larynx surgery, 502 in local anesthesia, 489 solution for, 480 in local jaw operations, 498 in mouth operations, 497 in nasal operations, 497 in neck surgery, 501 in operations on cheeks, 497 in operations on gums, 497 in outer ear operations, 497 in scalp wounds, 496 in thyroid operations, 503 in tongue excision, 497 in tracheotomy, 502 Schleich's, in spinal analgesia, 559 submental, in lower lip operation, 498 Infiltration anesthesia, anesin, in, 711 Barker's anesthetic in, 713 eucain-B in, 756 eucain lactate solution for, 758 solutions for, 693 Infusion in shock prevention, 403, 404 Inguinal glands, enlargement of, in status lymphaticus, 332 Inguinal hernia operation under co- lonic ether anesthesia, 454 under local anesthesia, 493 under spinal analgesia, 579, 580, 588, 591, 625, 626 Inguinal region, operations in, site of spinal puncture for, 610 Inhalation anesthesia, discovery of, 3, 7 Inhalation anesthetics, list of, based on safety to life, 325 therapeutic uses of, 666-674 Inhaler, Allis, 216 Bennett, 218 Esmarch, 217 Furniss gas-ether, 220 Gwathmey, 218, 219, 220 Hareourt's, 320, 321 Inhibition, cardiac, duo to chloroform, 302 Injection Hirsch, 768 Injection in spinal analgesia, technique of, 617-623 ' ' Inogen ' ' compounds in nervous sys- tem, effect of anesthesia on, 47 Inosit -mono -methyl ether as preserva- tive of chloroform, 292 Insane patients, anesthesia in, 331 chloroform indicated for, 310 psychic treatment for, preliminary to anesthesia, 366 Insanity following administration of anesthetic, 832 Insomnia after subarachnoid anal- gesia, 583 anesthetic treatment for, 667, 668 induction of electric sleep in, 633 use of hedonal in, 764 Instillation of cocain in eye surgery, 501 Insufflation, endopharyngeal. See En- dopharyngeal anesthesia endotracheal. See Intratracheal in- sufflation Insusceptibility to anesthetics, 832 Intestinal obstruction, anesthesia in, 356 in children, spinal analgesia in, 589 intratracheal insufflation in, 432 Intestinal operations under local anes- thesia, 518, 521 Intestinal tract, care of, preliminary to anesthesia, 365 Intestines, effect of temperature on, during anesthesia, 386 Intra-abdominal administration of oxy- gen, 89, 90-92 Intra-arterial anesthesia, 492, 493 Intralaryngeal operations under colonic ether anesthesia, 436 Intranasal operations, anesthesia in, 340 Intra-osseous injection of anesthetic solutions in dentistry, 547, 548 Intratracheal insufflation, apparatus for, 419 bibliography on, 432 course of anesthesia by, 429, 430 definition of, 416 history of, 416-419 in prevention of acapneal respiration, 409 indications for, 431, 432 statistics for, 843, 852, 855 technique of, 426-429 errors in, 430, 431 value of, as a method of artificial respiration, 432 Intravenous anesthesia, 523-534 administration of anesthetic in, 529, 530 after-treatment in, 530-532 apparatus for, 525, 530, 531 blood changes in, 533, 534 history of, 523, 524 mixed forms of, 532, 533 of extremities, 506, 509, 511 patient under, 530 physiology of, 524 preliminary narcosis in, 370, 524, 532, 533 selection of vein for, 525, 526 solutions for, 525, 529 922 INDEX Intravenous anesthesia, technique of, 524-532 urinary examination in, 534 Intravenous infusion in serious cases of shock, 404 Intussusception in children, spinal analgesia in, 589 lodin, preliminary use of, in oral sur- gery, 543 in post-operative vomiting, 379 in spinal injection, 617 in sterilization of skin, 615 tincture of, 692 Iodoform, 768 photochemical oxidation of, 888 lonone, as preservative of chloroform, 292 Iridectomy, use of chloroform in, 338 Ischemia in venous anesthesia, 490-492 of gut, 443 Isoamyl hydrocuprein, 805 Isoamyl nitrite. See Amyl Nitrite Iso-amylene-beta-pental, 768 Isobutyl, 805 Isobutyl ester of para-amidobenzoic acid. See Cycloform Isopon, 768. See also Pantopon Isopral, 768, 769 in intravenous anesthesia, 532 in preliminary medication for oil- ether colonic anesthesia, 461 Isopropyl, 805 Jaboulay on spinal analgesia, 558 Jackson, Charles T., 8, 12, 14, 16-19 Jackson's direct laryngoscope, 428 Jackson's speculum, 226 James' method of inducing hypnosis, 657 Janeway's apparatus for intratracheal insufflation, 423, 424 Jaundice following ethyl chlorid anes- thesia, 265 Jaw excision, under colonic ether anes- thesia, 435 under local anesthesia, 490, 498, 511 Jehnol, 769 Jessel and Orndorff, on preparation of chloroform from acetone, 874 Johimbin. See Tohimbin Jonnesco 's method of spinal analgesia, 562, 563, 576, 582, 583, 586, 591, 595, 597, 603, 604, 610, 622 mortality record in cases under, 597 site of spinal puncture in, 607, 608 Jonnesco 's stovain-strychnin solution for, 582, 603 Josson warmed ether vapor, 228 Jouanin on nirvanin, 781, 782 Juilliard's statistics, 854 Junker apparatus for chloroform ad- ministration, 321, 322 Junker chloroform bottle, 226 Junker inhaler, 24, 27, 228, 314 modification of, for ether by Braun, 178 Kandol. See Canadol Kappeler, on decomposition of chloro- form, 884 on ethyl acetate, 736 on morphin hydrochlorid, 779 Katharin. See Carbon tetraehlorid Keen's prevention of shock, 383, 404 Kelen, 250, 769. See also Ethyl chlorid Kelene, 537, 760 Kelene-methyl, 769 Kemp, experiments of, with nitrogen and nitrous oxid, 125 Keroselene, 769 introduction of, 24 Kessler, on purification of chloroform, 878 Ketopropane, 689. See also Acetone Kidney lesions, colonic ether anesthesia indicated for, 457 Kidney removal under local anesthesia, 519 Kidneys, care of, during anesthesia, 374 concomitant affections of, spinal analgesia contra-indicated in, 587 diseases of, anesthesia in, 330 ether contra-indicated in, 248 sequestration anesthesia in, 473 eifect of chloroform on, 303, 304, 309 effect of ether on, 189-191, 248 effect of nitrous oxid on, 132 effect of shock on, 385 effect of spinal analgesia on, 583 elimination of ethyl chlorid through, 264 fatty degeneration of, following re- peated administration of ethyl chlorid, 265 preliminary treatment of, dosage for, 364 Kinderjy on spinal analgesia, 561 Kit of anesthetist, 362, 363 Klapp 's technique for sequestration anesthesia, 471 Klikowitsch on nitrous oxid and oxy- gen, 670 Klose on spinal analgesia, 565, 571 Knee resection under colonic ether anesthesia, 454 Kocher on contraindications to ether, 248 on local versus general anesthesia, 485 on thyroid operation under local anesthesia, 502 Koenig's aether anaestheticus. See ^ther anaestheticus Kohler on death due to spinal anal- gesia, 598 KoUer, cocain advocated by, 536 , Keller's use of cocain in surgery, 478, 556 Konig on administration of ethyl chlorid, 269 INDEX 923 Konig on after-effects of ethyl chlorid anesthesia, 264, 265 Kreis's use of spinal analgesia in ob- stetrics, 560 Kreutzman on chloroform-oxygen, 27 Krogius's method of local anesthesia in circumcision, 514 Labor* hypnotism and, 648 Lachrymation, effect of anesthesia on, 60 Lactation, effect of ether, on, 191, 192 Ladd on toxic effects of etherization by the closed method, 102 Laewen on nerve-blocking, 511, 512, 519 Lambotte on stovain in spinal anal- gesia, 603 Lamella cocainae, 769 Laminectomy, intratracheal insufflation indicated in, 431 Langgaard on chloral chloroform, 876 on eueain lactate in local anesthesia, 757 Laparotomy, anesthesia during, 355, 356, 374, 375 eoloaie ether anesthesia contra-indi- cated in, 457 post-anesthetic abdominal distention after, 115 shock in, 389 under local anesthesia, 518 under rectal etherization, 435 under spinal analgesia, 595 Laryngectomy, intratracheal anesthesia indicated in, 432 Laryngology, ethyl aminobenzoate in, 737 local anesthesia in, 489 Laryngoscope, Jackson's direct, 428 Larynx, cocainization of, for intra- tracheal insufflation, 427 Larynx operations under colonic ether anesthesia, 454, 457 under local anesthesia, 502 under spinal analgesia, 587 Lassar-Cohn 's method of purifying ether, 868 Latham's measures for shock preven- tion, 403, 404 Laudanon, 769 Laughing gas. See Nitrous oxid Lavosier, oxygen studied by, 893 Laweh on novocain bicarbonate solu- tions, 786 on post-operative pneumonia, 70 on warmed ether vapor, 228 Lawrie's statistics on chloroform, 852, 853 Lead dioxid in purification of chloro- form, 879 Lecithin in case of acute mania, 669 Leduc and Eouxeau, experiments of, on electric anesthesia, 628 on electric resuscitation, 637 Leedham-Green 's use of spinal anal- gesia, 587 Leg, amputation of, shock in, 403 cross-section of, above ankle, 509 Legal status of physician, 678 Leggett 's apparatus for colonic ether anesthesia, 437, 441, 442, 444 Legislation, medical, early, 677, 678 Legrand on eucain-B, 754, 756 Leichter salzdther, 250. See also Ethyl chlorid Lennander on lack of sensation in pel- vic viscera, 488, 516, 517, 518 Leopold on spinal analgesia, 569, 570 Lerda on local anesthesia in reduction of fractures, 508 Letargin, 769 Letheon, 16, 536, 769 Leukemia, sequestration anesthesia contra-indicated in^ 470 Levi on use of carbon dioxid with anes- thetics, 99 Lewis pendulum swing, 246, 393-396. Liability of physician, 680-687 of specialist, 684, 685 Liebermann, tropacocain prepared by, 832 Liebig, chloral chloroform discovered by, 876 discovery of chloroform by, 871, 872 investigations of, on etherization, 862 Liebreich 's method of preparing chloral chloroform, 876 Light, effect of, on chloroform, 290, 295, 296, 883-889 on ethyl chlorid, 256 in adenoid and tonsil operations, 344 Light anesthesia, shock during, 389 Light chloroform anesthesia, 306 Light sleep, hypnotic, 654 Ligueu's apparatus for colonic ether anesthesia, 442 Lillie's theory of anesthesia, 50-55 Lime as preservative of chloroform, 291 Lime salts in the blood, sequestration anesthesia contra-indicated in, 470 Lingual nerve, anesthetization of, 550, 551 Linhart 's A. C. mixture, 769 Linhart's C. E. mixture, 769 Lip excision under local anesthesia, 498 Lipoid solubility theory of anesthesia, 37-40, 46, 47, 48 Lipoidemia, 47, 48 Lipoids, role of, in anesthesia, 43, 44 Lipomata, removal of, under local anes- thesia, 495 under spinal analgesia, 625 Liquid air, in dental anesthesia, 537 preparation of oxyge;i from, 894 Liquor angestheticus, 770 Liquor anodynus Hoffmani, 859 Liquor Hollandicus. See Ethylene chlorid Liver, diseases of, sequestration anes- thesia in, 473 924 INDEX Liver, effect of chloroform on, 304 effect of ether on, 189, 190, 198 effect of shock on, 385 excision of, 518 fatty, acidosis in, 415 fatty degeneration of, following re- peated administrations of ethyl chlorid', 265 Liver operations, shock in, 403 Local anes-ether, 856 Local anesthesia, 476-523 after-treatment in, 488 as applied in dentistry, 535-553 cocain, 538-543 cold, 537 ethyl chlorid, 537, 538 hypodermic method, 536, 537 history, 535, 536 technique of injection, 543-553 circumcision under, 513, 514 combined with general anesthesia, 488 general preparation and technique in, 486-488 history of, 476-488 in diseases of the lungs, 330 in eye surgery, 500, 501 in gastro-enterostomy, 356 in Graves' disease, 353, 354 in gynecology, 516 in heart disease, 329 in inguinal hernia, 519-623 in larynx surgery, 502 in neck surgery, 501, 502 in rectum surgery, 514, 515, 517 in surgery of genito-urinary system, 512 in surgery of head and neck, 496, 497 in thyroid operations, 502-505 in tracheotomy, 502 in treatment of nose and tonsils, 499, 500 indications and scope of, 484, 485 - infiltration method of, 489 mental iniiuence in, 651, 652 methods of, 488-493 mortality in, 478, 486 of abdomen, 516-519 of ear, 498, 499 of extremities, 506-512 of skin, 493-496 of thorax and breast, 505, 506 preliminary use of morphin in, 370 regional method of, 490 solutions for, in goiter operations, 503, 504 special application of, 493-523 statistics for, 842, 843, 844, 855 surface application method of, 488, 489 syringes and solution bottles for, 481 through physiological action of spe- cial drugs, 477, 478 versus general anesthesia, 485, 486 Local anesthetics; relation of general anesthetics to, 48 Locasemin, 770 Loco-dolor, 250, 537, 770. See also Ethyl chlorid Locomotor ataxia, anesthetic treatment for, 667 Loeffler on method of anesthetizing dental pulp, 552 London Medical and Chirurgical mix- tures, 770 Long, Crawford W., 8-10, 19, 177 Lotheissen, experiments of, on elimina- tion of ethyl chlorid, 263-265 Lotheissen 's method of administering ethyl chlorid and oxygen, 278, 279 Ludwig's angina under colonic ether anesthesia, 454 Lues, spinal analgesia contra-indicated in, 587 Luke and Ross, statistics of, on nitrous oxid and ethyl chlorid, 854 LuUius, Raymundus, 858 Lumbar anesthesia by magnesium salts, 770, 771 by tropacocain, 836, 837 Erhardt's solutions for, 735 use of cocain arabinate in, 726 use of tropacocain hydrochlorid in, 833 Lumbar pressure, measurement of, 583 Lumbar puncture, early experiments in, 557, 563 Lumbard's elastic mask holder, 202 Lumbard's glass nasal tubes, 229 Lumbard's rubber ether blanket, 202 Lungs, aeration of, during anesthesia, 376 concomitant affections of, spinal analgesia contra-indicated in, 587 diseases of, anesthesia in, 329, 330 ether contra-indicated in, 248 effect of ethyl chlorid on, 258 effect of moisture contents of air on, 77, 78 effect of nitrous oxid on, 128 excretion of ethyl chlorid through, 264 Lung abscess, drainage of, under local anesthesia, 505 Lung complications, post-anesthetic, abolition of, by rebreathing, 113, 115 Lung cyst removal under medullary analgesia, 575 Lung lesions, colonic ether anesthesia indicated in case of, 457 Lungmotor for induction of artificial respiration, 399 Lusk, 564, 621 on paralyses due to spinal analgesic agents, 584, 585 on spinal puncture, 605-607 Lycoperdon proteus. See Puff-ball INDEX 925 Lyman on puflf-ball, 804 Lymphatism, 331-337. See also Status lymphaticus Lymph-nodes, cervical, removal of, under local anesthesia, 498 MacFarlane, J. P., and Co., on chloro- form prepared from acetone, 882 Magnesium salts, 735, 770-772 Maier 's Eadikal-anasthetikum. See Eadikal-anasthetikum Maier Malartic on spinal analgesia in obstet- rics, 593 Malherbe's method of administering ethyl chlorid, 272 Malpractice, 682-684 criminal, 686 Management of ordinary cases, after- treatment in, 378, 379 preliminary treatment in, 364-374 treatment during anesthesia in, 374- 378 Management of unusual cases, 379- 414, 415 idiosyncratic difficulties in, 382 muscular difficulties in, 381 nervous difficulties in, 381 post-anesthetic toxemia in, 382, 413- 415 respiratory difficulties in, 380, 381 shock in, 383-413 Mandibular foramen, location of, 549 Mandibular nerve, anesthetization of, 551 Mandragora, 2, 282, 477 Mania, acute, anesthetic treatment for, 668-670 Mannin, 772 Manometer, safety valve water, for colonic ether anesthesia, 444, 446, 451 Manual means of artificial respiration, 393 Marcille on ether irrigation of abdo- men, 672 Martin, E. D., on cocain in spinal anal- gesia, 600 Martindale's mixture, 689, 772 Martmeyer, ether introduced into com- merce by, 859 Marx on spinal analgesia, 560, 593, 600 Mask, Boothby and Cotton, for nitrous oxid-oxygen anesthesia, 166 Ferguson, 203 Gwathmey-Woolsey, for nitrous oxid- oxygen anesthesia, 172 Meltzer 's, for artificial respiration, 400 usual ether, 202 Yangauer, 203 Massage, cardiac. See Cardiac Mas- sage Masseter muscles, contraction of, under ethyl chlorid, 261, 262 Masson's method of purifying chloro- form, 880 Mastoid operation, anesthesia in, 339 colonic ether, 454 local, 499 Matas, afjparatus of, for hypodermic injection, 484 on cocain, 478, 482, 490, 497 on limitations in use of spinal anal- gesia, 586 Mathews-Brown theory of anesthesia, 42-44 Mayos' administration of ether, 203- 205 Mayos' stripping procedure under local anesthesia, 511 Mayow, oxygen prepared by, 893 Maxillae, operations on, chloroform in- dicated for, 310 McKesson, blood-pressure apparatus of, 409, 411 blood-pressure chart of, 412 method of, for anticipating shock, 410-413 Measure dropper for ethyl chlorid, 256 Mechanical causes of psychic shock, 384 Medical Pneumatic Institute, organiza- tion of, 4 Medical treatment preliminary to anes- thesia, 26, 370-378 ' ' Medicated Vapors, ' ' by Humphrey, 7 Medico-legal status of the anesthetist, 675-687 Medullary anesthesia by tropacocain hydrochlorid, 834 Meissner on novocain in spinal anal- gesia, 604 Meltzer, devices of, for artificial res- piration, 399-401 experiments of, with magnesium salts, 770-772 method of, for ether vapor adminis- tration, 238 Meltzer apparatus for intratracheal in- sufflation, 417 Meltzer pharyngeal tube, 400 Meltzer and Auer, experiments of, with intratracheal insufflation, 416- 419 Meningism after stovain anesthesia, 583 Menstrual period, anesthesia during, 355 Mental condition, influence of, on hyp- notism, 656 Mental depression, fatal effects of, 368 Mental foramen, location of, 551 Mental influence in anesthesia, 644-665 hypnosis, 653-665 hypnotism, 644-649 suggestion, 649-653 Mental suggestion in adenoid and ton- sil operations, 341 in anesthetizing children, 327 926 INDEX Menthol as preservative of chloroform, . 292 petrolatum and, as a spray, preceding adenoid and tonsil operations, 341 Menthol thymate, 772 Mentholated chloral, 723 Menthophenol, 772 Menthophenol cocain, 772. See also Bonain Mentin's method of purifying chloro- form, 879 Merck on soninoform, 819 Mering and amylene hydrate, 699 von Mering 's mixture, 772. See also Dimethylacetal Mesenteric glands, enlargement of, in status lymphaticus, 332 Mesmerism, 2, 4 Meta-amido-para-oxybenzoate of methyl. See Orthoform-new Metacetone, 804 MetEethyl, 772. See also Meth-ethyl Metal containers for ethyl chlorid, 255, 256 Metaldehyd, 689 Metallic chlorids in chloroform, 285 Meta-nitro-cocain, 688 Metatarsals, deep injection between, 510 Methaform, 711, 772, 773. See also Chloretone Methane, 773 preparation of chloroform from, 875 Methene chlorid, 777 Methenyl trichlorid, 281. See also Chloroform Methenyl-o-anisidin, 773 Methenyl-p-phenetidin, 773 Meth-ethyl, 537, 773 Methoxycaffein, 773 Methyl acetylsalicylate, 773 Methyl alcohol, 773, 774 in chloroform, 285, 692 Methyl bromid, 774 Methyl chlorid, 774, 775 combined with ethyl bromid and ethyl chlorid (somnoform), 276 for local anesthesia in dentistry, 537 presence of, in ethyl chlorid, 252, 253 Methyl chlorid-alcohol, 775 Methyl chlorid-ether, 775 Methyl chloroform, 832. See also Trichlorethane Methyl cinnamenylacrylate, 775 Methyl dichlorid, 775, 776 Methyl ether, 776 Methyl fluorid, 776 Methyl hydrate or hydroxid. See Methyl alcohol Methyl iodid, 776 Methyl oxid, 776 Methyl salicylates as preservative of chloroform, 292 Methylacetyl, 689. See Acetone Methylal, 776, 777 "Methylated" alcohol, ether prepared from, 861, 862 "Methylated" chloroform, 873, 874 * ' Methylated spirit, ' ' preparation of chloroform from, 285, 873, 874 Methylene, 777 Methylene bichlorid, 777. See also Narcotil Methylene chlorid, 777, 778 Methylene dimethylate, 776, 777 Methylene- dimethyl ester, 776, 777 Methylene ether, 778 Methylethyl, 778 Methylic ether, 861, 862 Methylic-ethylic ether, 778 Methylium bichloratum Eichardson. See Methylene ether Methylium oxyamidobenzoicum, 778 Methylpropylcarbinolurethane, 763, 778 Methyl-protocatechnique aldehyd, as preservative of chloroform, 292 Meyer on anesthol, 276-278 on "M. S.," 779 Meyer's angesthol, 702-711 Meyer's tropacoeain solution for spinal analgesia, 601 Meyer- Overton theory of anesthesia, 37-40 M.-H.-C. anesthesia, statistics for, 843 Michelson on spinal analgesia, 564, 570, 598 Micturition, involuntary, in nitrous oxid anesthesia, 132 Midy's mixture, 778 Milk, prohibited preceding adenoid and tonsil operations, 340 Miller on method of anesthetizing den- tal pulp, 552 statistics of, on ethyl chlorid, 850 Milne, open method of administering ethyl chlorid advocated by, 272 Minor surgery, intravenous anesthesia in, 492 Mitchell, James F., on local anesthesia, 476-523 on nerve injuries, 558 Mitchener and Hyndham, on magnesium sulphate, 771 Mitscherlich on chloroform, 873 theory of, of manufacture of ether, 862, 863 Mohr apparatus for rectification of ether, 864 Moisture, effects of, on anesthetics, 76- 80 Molars, technique of periosteal injec- tion of anesthetic solution about, 545 Molecular solution. See "M. S." Moles, removal of, under local anes- thesia, 495 Monobromethane, 738-748. See also Ethyl bromid Monochlorethane, 748. See also Ethyl chlorid INDEX 927 Monochlorethylene chlorid, 750 Mono-chlorethylidene chlorid, 832 Monochlorinated dutch liquid, 750 Monochloro-ethylene chlorid, 831, 832. See Ethylene chlorid Monochloromethane, 250. See also Ethyl chlorid Mono-iodoethane, 748 Moore-Eoaf theory of anesthesia, 44- 46 Morel's apparatus for colonic ether anesthesia, 442 Morphin, 463, 464, 465 administration of, during anesthesia in status lymphaticus, 334 as preservative of chloroform, 292 contra-indications to, 373 doses of, 372 for acid intoxication, 414 for adenoid and tonsil operations, 341 for anesthol administration, 277, 705 for colonic ether anesthesia, 450, 454 for ether anesthesia, 207, 208 for ethyl chlorid anesthesia, 262, 277 for intratracheal anesthesia, 427 for local anesthesia, 486 for nitrous oxid-oxygeu anesthesia, 165 for oil-ether colonic anesthesia, 461 for spinal analgesia, 558, 581, 592, 612 effect of, on ether elimination, 108 in administration of chloroform, 314 in case of acute mania, 669 in emergency treatment, 363 in goiter, 354 in intravenous anesthesia, 524, 533 in post-operative treatment, 377 in preliminary medication, 328-331, 339, 369, 370, 371, 412, 847 in prevention of acapnia, 409 in rectal cases, 355 with chloroform, 26 Morphin-anesthol-ether sequence, 209 Morphin hydrochlorid, 778, 779 Morphin, hyoscin, and cactin, 768. See also H. M. C. Morphin injection before operation, 482 in neuralgia, 478 in shock prevention, 403 Morphin poisoning, electric resuscita- tion in, 643 Morphin-scopolamin, 108, 811-817 decrease in post-operative pneu- monias under, 199 prophylactic use of, with ethyl chlorid anesthesia, 262, 263 Morphin sulphate injection in local anesthesia, 486 Morphinism, chronic, acidosis in, 415 Morson on effect of air on ebloroform, 883 Mortimer on chloroform, 414 on contra-indications to ether, 248 Morton, William T. G., 11-14, 16, 17, 18, 177 first demonstration of surgical anes- thesia by, 13 on spinal analgesia, 562 cases of, 574 Morton inhaler, 13, 14 Morton's "letheon," 536 Motor paralysis from Esmarch elastic bandage, 477 in venous anesthesia, 492 Mouth, disinfection of, preliminary to anesthesia, 364 effect of shock on, 385 operations on, colonic ether indicated in, 457 ether for, 247 intratracheal insufflation for, 431, 432 local anesthesia for, 497 rectal etherization for, 435 sequestration anesthesia for, 471 with Sutton's colonic anesthesia apparatus, 450 Mouth-gag, 362 Hewitt-Mason 's, with anesthetic tubes, 322 in artificial respiration, 393 in epileptics, 331 in ethyl chlorid anesthesia, 274 in intratracheal anesthesia, 427 "M. S.," 704, 709, 710, 779 Mucous glands, effect of anesthesia on, 60 effect of warming the anesthetic on, 70 Mucus, secretion of, after ether, 189, 199 Miiller, on use of oxygen with anes- thetics, 86-88 theory of, of anesthesia, 36, 37 of ethyl chlorid anesthesia, 260, 261 Mulzer, experiments of, with ether upon the blood, 186, 187 Murphy on spinal analgesia, 561, 586, 604 Muscular changes due to psychic shock, 385 Muscular flaccidity in overdose of ethyl chlorid, 261 Muscular phenomena during anesthesia, 381, 385 Muscular relaxation or rigidity in ethyl chlorid anesthesia, 263 Muscular system, effects of anesthetics on, 59, 60 effects of chloroform on, 302, 303 effects of ether on, 189 effects of ethyl chlorid on, 261 effects of nitrous oxid on, 131 Mylocal, 779 ' 928 INDEX Myocarditis, sequestration anesthesia contra-indicated in, 473 Myogram traces showing muscle-nerve reaction, 629, 631-633 "Nabolis," 536 Nalicin, 779 Naphtha, 860 Naphthalene,- 714 Nasal operations under rectal etheriza- tion, 435 Narcoform, 779 Narcophin, 780 Narcosin, 780 Narcosis, distinguished from anesthesia, 50 Narcotil, 780 " Narkose-gemisch " Dr. Hirschlaff, 780 Nasal anesthesia with nitrous oxid-oxy- gen, in aural surgery, 173 in obstetrics, 173 Nasal catarrh, use of orthoform-new in, 789 Nasal inhaler, Teter, 155, 156 Nasopharyngeal tubes for nitrous oxid and oxygen, Teter 's, 157 Natural gas, preparation of chloroform from, 875 preparation of ether from, 862 Nausea after colonic ether anesthesia, 438, 458, 464 after ethyl chlorid anesthesia, 264, 338 after use of nitrous oxid, 132 due to cocain, 539 in spinal analgesia, 577, 582, 583, 595 post-anesthetic, 113 effect of oil of bitter orange peel on, 94 effect of warming the agent on, 70 treatment for, 379 preliminary medication in, 373 prevention of, during anesthesia, 374 Nealpon, 780 Neck, operations on, colonic ether anes- thesia indicated in, 457 intratracheal insufflation indicated in, 431 under local anesthesia, 501-505 under spinal analgesia, 597 swelling or engorgement of, nitrous oxid contra-indicated in, 338 Necrosis, due to prolonged freezing in dental anesthesia, 537 Nef's bivalent carbon hypothesis, 42, Negroes, importance of psychic influ- ences in anesthetizing, 651 Neidle's experiments on heat generated by chloroform-ether mixture, 706-710 Nephritis, anesthesia in, 374 dosage of hyoscin in, 815 Nephritis, preliminary medication by morphin, contra-indicated in, 373 spinal analgesia in, 580, 587 Nephropectomy under spinal analgesia, 560 Nephrotomy under colonic ether anes- thesia, 454 Nerve block in local anesthesia, 497, 498, 513 of arm, 507 of face, 497 in skin grafting, 511 Nerve centers, effect of aliphatic hy- drocarbons on, 689 specific action of nitrous oxid on, 125-127 Nerve corpuscles in anesthesia, 33 Nerve fibers in anesthesia, 33 Nerve tissue, effect of ethyl chlorid on, 261 Nerve trunk injection, solution for, 480 Nervocidin, 780, 781 Nervous patients, choice of anesthetic in, 330 Nervous phenomena during anesthesia, 381 Nervous system, anesthetic treatment for extreme irritability of, 667' effect of anesthesia on, 61, 62 effect of chloroform on, 302 effect of ether on, 188 effect of ethyl chlorid on, 260, 261 effect of nitrous oxid on, 131 post-operative effects of spinal anal- gesia on, 582 Nessler 's reagent, in testing chloro- form, 890 Netter on magnesium salts, 771 Neudorfer on chloroform and oxygen, 26 Neuralgia, chloral-menthol in, 723 differentiation of, from neuritis, by ethyl chlorid, 670 from visceral diseases, by ethyl chlorid, 671 ethyl chlorid in treatment of, 670 injection of morphin in, 478 Neurasthenia, use of hedonal in, 764 Neurocain, 781 Neuroglia, in anesthesia, 35, 36 Neuroregional anesthesia in inguinal hernia, 519-523 local method of, 478 of extremities, 506 Neurorrhaphy under colonic ether anes- thesia, 454 Neurotic patients, preliminary medica- tion in anesthetizing, 371 under spinal analgesia, 591 Nicloux on ether elimination, 196 on the passage of ether from mother to fetus, 191 Niemann 's discovery of cocain, 555 Nirvanin, 540, 781, 782 in spinal analgesia, 563, 599 INDEX 929 Niter in preliminary treatment of kid- neys, 364 "Nitric "ether," 749 Nitrobenzene as preservative of chloro- form, 292 Nitrogen, 782, 78;] Nitrogen monoxid. See Nitrous oxid Nitrogen protoxid. See Nitrous oxid Nitroglycerin injection in spinal anal- gesia, 581, 592, 612, 625 "Nitrous ether," 749 Nitrous oxid, 692, 783 administration of, 136-175 alone, 137 apparatus for, 136 dangers of, 136, 137 Guedel aj^paratus for, 138, 139, 140 precautions in, 137-139 as a sequence to ether, 141, 142, 143 by intratracheal insufflation, 429 rebreathing in, 105-144 with air, 136, 137, 142 advantages of oxygen over, 143, 144 in unknown quantities, 140, 141 in definite amounts, 141 safety of, 325 with chloroform-ether, 142, 143 with oxygen. See Nitrous oxid and oxygen after-effects of, 135 analysis of, 122 causes of death from, 132 chemical properties of, 121 comparison of, with other agents, 135 contra-indicated, in ophthalmic cases, 338 . danger of shock with, 388 deoxygenation or asphyxiation theory of action of, 124, 125 discovery of, 4, 10 early use of, by Humphrey Davy, 5 in dentistry, 118, 119 effect of, on blood pressure, 59 on circulatory system, 128-131 on glandular system and other structures, 131, 132 on muscular system, 131 on nervous system, 131 on respiratory system, 127, 128 elimination of, from the blood, 134, 135 ethyl chlorid and, 279 ethyl chlorid compared to, 266, 267, 849 for anesthetizing children, 327 for short operations, 338 history of use of, 118-120 hyperoxygenation theory of action of, 123, 124 impurities of, 121, 122 in adenoid and tonsil cases, 340 in convulsions from poisoning, 667 in dentistry, 11, 24, 537 Nitrous oxid in fracture reduction un- der local anesthesia, 508, 509 in gastro-enterostomy, 356 in goiter, 353, 354 in insanity cases, 381 in local liucsthesia of abdouion, 518 in nervous patients, 330 in 2:)aracentesis of membrana tym- pani, 339 indications and contra-imiications for, 135, 136 insusceptibility to, 832 introduction of, into England, 24 liquid, 120 in dental anesthesia, 537 manufacture of, 121 method of heating, 136 overdose of, symptoms of, 167 physical properties of, 120, 121 preliminary use of, 388 special physiology of, 123-135 specific action of, on brain cells, 125 stages of anesthesia with, 132-134 standard of purity of, 122, 123 statistics for, 843, 844, 855 Stockman and, 5 use of scopolamin-morphin with, 816 wdth air and ether, statistics of, 856 with ether, 25 with ethylene chlorid, 749 Nitrous oxid and oxygen, 24, 80, 81, 119, 120, 143-175 administration of, Davis' method of, 151 endopharyngeally, 159, 160 Gatch's method of, 144-151 Gwathmey-Woolsey method of, 171-175 Hewitt's method of, 151-153 Teter's method of, 153-159 with oxygen, in definite quantities, Boothby and. Cotton method of, 160-170 with oxygen in indefinite quanti- ties, 144 with rebreathing, 104-144 advantages of, 143, 144 combined with ether, 164, 165, 167, 168, 172 statistics for, 855, 857 combined Avith ethyl chlorid, 325 combined with warm ether, 325 contra-indications to, 328 brain operations, 354 effect of warming on, 64-66 effect of, on heart action, 670 for endotracheal work, 173 for patients between 19 and 50, 328 in anemic convulsions, 667 in cancer, 330 in curettage, 355 in diabetes, 330 in diagnosis, 667 in kidney diseases, 330 in obstetrical cases, 355 930 INDEX Nitrous oxid and oxygen in paracen- tesis of the pericardium, 329 in rectal cases, 355 in respiratory diseases, 330 in short operations, 338 in tuberculosis, 329 premedication in, 165 safety of, 325 statistics for, 843, 844-847, 855, 857 therapeutic uses of, 670 use of, in Gatch's apparatus, 104, 107 Nitrous oxid anesthesia, 404 exhaustion under, 405 Gatch's method of, 103-115 acapnia in, 112 basis of technique of, 105 clinical results of, 108, 109 fatalities from, 110 hypereapnia in. 111 in cardiac cases, 111 in long operations, illustrative cases of, 109 maintenance of ether balance in, 106 Nitrous oxid-anesthol, statistics for, 843 Nitrous oxid-ether sequence, 218-320, 240, 325 followed by ether, 325 followed by ether and chloroform, 325 in genito-urinary operations, 355 in laparotomy, 355, 356 in mastoid operations, 339 inhalers for, 218-221 introduced by Clover, 177 statistics for, 843, 848, 855, 857 technique of, 221 Nitrous oxid-ether-anesthol, sequence, statistics for, 843, 855 Nitrous oxid-ether-chloroform sequence, 223-224 statistics for, 843, 851, 852, 855 Nitrous oxid-ether vapor sequence, diagrammatic sketch of, 245 Nitrous oxid-ethyl chlorid-ether se- quence, 325 Nitrous oxid-oxygen-ether sequence, 325 Nitrous oxid-oxygen-ether-chlorof orm se- quence, statistics for, 855 Nopain, 783 Nor-cocain, 783 Northrop on oxygen and chloroform, 27 Nose, care of, preliminary to anesthesia, 364 closure of alee of, during anesthesia, 389 operations on, alypin in, 693 ether for, 247' eucain lactate solution for, 758 under local anesthesia, 497 treatment of, under local anesthesia, 499, 500 Novadrin, 783 Novocain, 691, 692, 783-786 atoxyl and, 818 in anoci-association, 370 in anesthesia of scalp, 497 in gastroenterostomy, 356 in goiter operations, 354 in hypodermic tablets, 604 in local anesthesia, 478, 482, 483 in dentistry, 540, 541 in oil-ether colonic anesthesia, 463 in spinal analgesia, 563, 571, 576, 599, 603, 604 in venous anesthesia, 490 statistics for, 842 Novocain, adrenalin, and sodium bicar- bonate, 786 Novocain and epinephrin, statistics for, 841 Novocain bicarbonate solutions, 786 Novocain infiltration in general anes- thesia, 485 in venous anesthesia, 491 Novocain injection along line of in- cision in shock prevention, 406 Novocain nitrate, 786, 787 Novocain solutions, 482, 483 for arterial anesthesia, 492 Novocain tablets, 818 Novocain-adrenalin for dental anes- thesia, 540-542 Novocain-suprarenin injection of Gas- serian ganglion, 498 Novocain-suprarenin solution, 787 in anesthesia for fractured clavicle, 506 of urethra and bladder, 512 in removal of cervical lymph-nodes, 498 in thyroids operations, 505 Novocain-suprarenin tablets, 787 Novoconephrin, 787 Novo-dentsesthin, 787 Novorenal, 787 Novorobiol, 808. See also Eobiol Nunneley, T., 713, 717, 719, 720, 738, 837 Nussbaum, 779 Nussbaum's mixture, 689, 787 Nux vomica, tincture of, in dietetic shock, 387 Obalgo, 788 Oberst's regionary anesthesia, anesin in, 711 Obese patients, chloroform indicated for, 310 choice of anesthetic in, 329 Obstetrics, anesthesia in, 355 chloroform anesthesia in, 20-22, 310, 368 ethyl chlorid anesthesia in, 266, 268 hyoscin-morphin mixture in, 768 hypnotism and, 647, 648 nitrous oxid-oxygen anesthesia in, 173 Otis mixture in, 798 INDEX 931 Obstetrics, scopolamin-morphin injec- tions in, 813, 815, 816 spinal analgesia in, 560, 587, 593, 594 Townley's anodyne mixture in, 831 Obtundo, 788 Occupation and surgical shock, 384 Octane, 788 Odiot, 788 Odor, anesthetic, elimination of, 93, 207, 208 Offergeld on effect of ether vapor en the lungs, 101 Offergeld and Miiller, experiments of, with animals, 335, 336 Ohio mojiovalve, 158-16.0 Ohio small nitrous oxid inhaler, 159 Oil absinthium, 788 Oil of bitter orange peel, use of, pre- ceding anesthesia, 60, 92-96 in anesthol-ether sequence, 847 in children, 327 in chloroform administration, 313, 316 in chloroform-ether sequence, 207, 847 in circumcision, 355 physiological basis of, 95, 96 Oil of bitter orange peel-ether se- quence, 240 statistics for, 843, 852, 855 "Oil of wine," 864 Oil wormwood, 788 Oil-ether colonic anesthesia, 458-466 administration of, 461 animal experimentation with, 458-460 apparatus for, 460 cases of, 463-466 history of, 458 oil-ether mixture for, 461, 463 physiology of, 462, 463 preliminary preparation for, 460- 463 Old age. See Aged Olefiant gas, 736 Olive oil, 463 administration of, during anesthesia, 376, 379 in case of acute mania, 670 in preliminary medication for oil- ether colonic anesthesia, 461 Oliver and Garrett, on hyperoxygena- tion theory of nitrous oxid, 123, 124 Omnopon, 798-800. See also Pantopon Open method, administration of ethyl chlorid by, 272 effects of, on lungs, 101, 102 use of, in heart disease, 329 Ophthalmology, alypin in, 693 chloroform in, 338 enophthalmin as antiseptic in, 735 ethylene chlorid in, 749 eucain-A in, 754 eucain lactate solution for, 758 local anesthesia in, 489 Ophthalmology, novocain in, 784 tropacocain hydrochlorid in, 833 O-phthaloyl-bis-methylecgonin, 788 Opiopon, 788 Opisthotonos, due to ethyl chlorid, 261 Opium, deodorized tincture of, in 'post- operative vomiting, 379 preliminary use of, 653 Opium poisoning, insufflation of pure air or air and oxygen in, 432 Opon, 788 Oppenheimer 's anaestiform, 710 Opposition to anesthesia, theological, 21 Opsonic index, restoration of, by olive oil administration, 376 Orange, peel. See Oil of bitter orange peel Orchidopexy under colonic ether anes- thesia, 454 Ormsby 's statistics, 854 Orndorff and Jessel, on preparation of chloroform from acetone, 874 Ortho-chlor-cocain, 688 Orthoform, 699, 737, 788 in spinal analgesia, 563 Orthoform-new, 788-797 in spinal analgesia, 599 Orthoform-new hydrochlorid, 797 Orthonal, 797, 798 Orthopnea, colonic ether anesthesia contra-indicated in case of, 457 Osgood on toxic effects of etherization by the closed method, 102 Osmotic concentration of the blood in anesthesia, 45 Osteopaths, 675 Osterhout, experiments of, 40 Otis mixture, 798 Otte on after-effects of ether, 199 Ouabain, 798 Ovary operations, shock in, 403 Over-anesthesia, 371, 386, 413 Overdose, 402, 464, 465 in anesthetic shock, 388 in anesthol anesthesia, 277 in colonic ether anesthesia, 439, 452 in ether narcosis, 195 in ethyl chlorid anesthesia, 263 in nitrous oxid anesthesia, 134 in oil-ether colonic anesthesia, 462, 463 in spinal analgesia, 597 of chloroform, 305, 308 Overdose stage in anesthesia, 381 Overton. See Meyer-Overton Oxid of ethyl, 178 Oxygen, air and, insufflation of, as a method of artificial respiration, 432 as an anesthetic, 798 as preventive of post-anesthetic shock, 376 as vehicle for ether vapor in rectal anesthesia, 441, 442, 452, 455, 456 932 INDEX Oxygen, combination of, with anes- thetic agent, 80-89 experiments on, 82-86 discovery of, 4 effect of, on intestines, 114 on veins and arteries, 114 ethyl chlorid and, 278, 279 history of, 893 impurities in, 894 in adenoid and tonsil operations, 343 in chloroform administration, 294, 295, 314, 317 increase of, in shock prevention, 403 intestinal absorption of, 434 intra-abdominal administration of, in connection with anesthesia, 89- 92 methods of manufacturing medi- cinal, 893, 894 nitrous oxid and. See Nitrous oxid and oxygen purity of commercial medicinal, 895 standards of purity for, 895 supply of, essential in all nitrous oxid operations, 338 with carbon dioxid in treatment of acapnia, 409 with chloroform by Harcourt 's in- haler, 321 ' ' Oxygen enemata ' ' in colonic ether anesthesia, 453 Oxygen-ether mixture in colonic anes- thesia, 444, 446 Oxygen-ether vapor, administration of, 239, 240 in mastoid operation, 339 Oxysparteinum hydrochlorid, 798 Oxyuris vermicularis, use of guaiasa- nol in, 763 "Paid anesthetist system," 676 Pain, abdominal, in colonic ether anes- thesia, 435_, 436, 455 acute, anesthetic treatment for, 666, 667 in spinal analgesia, 578 localization of, with ethyl chlorid, 671 post-operative, effect of preliminary medication on, 371 gas, prevention of, 405, 406 in local anesthesia, 483 Painless surgery, first demonstration of, by Morton, 12 Pallor due to shock, 385 in administration of chloroform, 308, 309, 313, 315 in chloroform anesthesia, 389 in overdose of ethyl chlorid, 261 in spinal analgesia, 581, 582 Panacea vitrioli, 859 Panhysterectomy under spinal anal- gesia, 581 Pantopon, 798-800 preliminary medication with, in ether narcosis, 208 Pantopon-scopolamin anesthesia, 817 Papilloma of neck, operation on, under spinal analgesia, 625 Para-amidobenzoic acid ethyl ester, 801 Paracentesis of membrana tympani, anesthesia in, 339 of pericardium, choice of anesthetic in, 329 under local anesthesia, 499 Paraffin in purification of chloroform, 879 Paraldehyd, 689, 800, 801 in intravenous anesthesia, 533 in preliminary medication in oil- ether anesthesia, 461 Paralysis due to aromatic hydrocar- bons, 689 due to spinal analgesic agents, 584 Paramidobenzoic acid ethyl ester, 737, 738 Paranephrin, 801 Paranephrin-cocain mixture, 801 Paranephrin-cocain-subcutin, 801 Paranephrin-novo-subcutin, 801 Para - oxy - meta - methoxyallyl-benzene, 759 Para-phenol sulphonate of ansesthesin, 829 Para-phenol sulphonic acid of para- amidobenzoic acid ethyl ether, 829 Pareses, motor, in spinal analgesia, 582, 583 Parotid tumor removal under colonic ether anesthesia, 454 Parturition, use of ethyl chlorid in, 266. See also Obstetrics Passy on odorous power of various sub- stances, 93, 94, 889 Pasteurization in Babcock's diffusible solution for spinal analgesia, 605 Pate de vido, 801 Patterson on spinal analgesia, 577, 581 Patton's "Anesthesia and Anes- thetics," 11, 16 Pelvic cellulitis case under oil-ether colonic anesthesia, 463 Pelvic operations under spinal anal- gesia, 586, 597 Penis, effect of shock on, 386 Pental, 698, 801, 802 statistics for, 853 Pentan-2-ol-urethane, 763 Pentane, 802 Pentene, 697. See also Amylene Pentylene. See Hydramyl Perchlorethane in chloroform decompo- sition, 295 Perchlorethylene in chloroform de- composition, 295 Perchlorid of formyl, 281. See also Chloroform Pericardium, tapping of, under local anesthesia, 505 Pericementitis, injection of anesthetic solution in, 547 INDEX 933 Pericementitis, use of ethyl chlorid eon- ti'a-indieated in, 538 Peridental anestliesia, 547 Perineum operations, under spinal analgesia, 587, 597 site of spinal puncture for, 610 Perineural injection of anesthetic solu- tions in dentistry, 548-552 in extremities, 506, 507 in local anesthesia, 490 in lower lip operation, 498 of posterior tibial nerve, direction of needle in, 509 Periosteal injection in local anesthesia of mastoid process, 499 Periosteum, anesthetization of, 476, 496 injection of, 511 in local a,nesthesia, 509 in lower jaw operations, 498 Peritoneal infections, ether treatment in, 671, 674 Peritoneum, effect of shock on, 386 parietal, local anesthesia of, 516- 518, 521 visceral, lack of pain sense in, 517 Peritonitis, administration of fluid per rectum in, 375 anesthesia in, 356 with drainage, 375 Permeability of cell membranes, anes- thesia and, 53-55 Peronin, 715, 802 Peroxids, in preparation of oxygen, 894 presence of, in ether, 867 Personality of anesthetist, 652 Personne, on decomposition of chloro- form, 884 Peterka's figures on ethyl chlorid, 849 Petrolatum with menthol, as a spray, preceding adenoid and tonsil op- erations, 341 Petroleum, preparation of ether from, 862 Petroleum spirit, 284 Pharmacopoeia Helvetica, ethyl chlorid tests prescribed by, 258 Pharyngeal insufflation with ether, sta- tistics of, 856 Pharyngeal tube, 390, 391 Connell's, 392 Ferguson 's, 391 Hewitt's, 390 in nose and mouth operations, 234 Meltzer 's for artificial respiration, 400 Pharynx operations, colonic ether indi- cated in, 457 Phenetidy-acetphenetidin hydrochlorid, 765 Phenol, 692, 718. See also Carbolic acid Phenol camphor. See Camphor, phenyl- ated Phenolcocain, 726. See also Cocainum phenylicum Phenolphthalein in testing chloroform, 890 in testing ether, 866 I'henylacetyl, 688 I'henyl-urethane, 802, 803 Phenyphrin, 803 Plilebitis following sequestration anes- thesia, 473 Phoenixin. See Carbon tetrachlorid, 803 Phosphorus pentoxid, in preparation of ethyl chlorid, 252 Phthisis, anesthesia in, 330 nitrous oxid anesthesia contra-indi- cated in, 136 Physician, civil liability of, 681 criminal liability of, 685 ethical liability of, 680, 681 liability of, growing out of gross ig- norance or negligence, 685, 686 qualifications of, 679 statutory liability of, 686, 687 Physiologic rest in treatment of shock, 404 Physiology of cerebrospinal fluid, 563 of chloroform, 297-310 of inhalation anesthetics, in general : effects of inhalation anesthetics upon various parts of the organ- ism, 56-62 introductory remarks, 30-32 modifying factors, 62-99 theories of the action of general anesthetics, 32-56 of intravenous anesthesia, 524 of oil-ether colonic anesthesia, 462- 463 Pictet chloroform, 877, 880, 881 Pilling chloroform dropper, 312 Pinneo's ether vapor apparatus, 234, 235 Pinneo 's mouth tube for continuous vapor anesthesia, 236 Piperidin, 804 Piperonal, 688 Pitha, use of morphin hydrochlorid by, 779 Pituitary extract injection in cases of shock, 404 Plasma cells of the neuroglia, in anes- thesia, 36, 37 Plasma-membranes, role of, in anes- thesia, 53-55 Plecavol, 803 Pleistopon, 803 Plethoric patients, preliminary medica- tion in anesthetizing, 371 Pleura, aspiration of, under local anes- thesia, 505 Pleurisy, anesthesia in, 329 chloroform indicated for, 310 "Pneumatic Institute," 118 Pneumonia after ether, 189 anesthesia in, 329, 330 from aspiration during anesthesia, prevention of, 364 934 INDEX Pneumothorax, intratracheal insuffla- tion in, 418 Poggiolini on blood changes in anes- thesia, 58 "Poho oil," 807 Poisoning, chloroform. See Chloroform poisoning due to cocain, cause of, 478, 479 nitrous oxid-oxygen in seizures from, 667 opium, 432 Pollock, on chloroform, 25 Polychloral, 803 Polyehlorated hydrochloric ether, 748. See also Ethyl chlorid poly- ehlorated Pompilian, Mile., experiments of, on electric anesthesia, 628 Popliteal glands, enlargement of, in status lymphaticus, 332 Popov, on influence of light on chloro- form, 886 Poppert on effect of ether vapor on the lungs, 101 Poppy-seed oil as preservative of chloroform, 292 Porter on the trained anesthetist, 676 Post-anesthetic pneumonia, effect of warming the agent on, 70 Post-anesthetic toxemia, 413-415, 832 Post-mortem examination in status lymphaticus, 335 Post-operative gas pains, causes and prevention of, 405, 406 Posture during local anesthesia, 486 during oil-ether colonic anesthesia, 461 during sequestration anesthesia, 470 during spinal analgesia, 613, 614, 625 for adenoid and tonsil operations, 345-352 Potassium hydroxid, in testing chloro- form, 890 in testing ether, 866 Potassium permanganate in disinfec- tion of mouth, 364 Potassoeain, 803 Pregnancy, electric analgesia contra-in- dicated in, 635 Preliminary medication, dosage for, 372, 373 importance of, 369, 370 in intravenous anesthesia, 524, 532, 533 in oil-ether colonic anesthesia, 460, 461 in thyroid operations under local anesthesia, 502 indications and contra-indications of, 373 lack of, ill effects of, 381 rules for, 371, 372 time for giving, 372 See also Morphin and Atropin Preliminary treatment in ordinary eases, 364-374 Preliminary treatment, hygienic, 364-366 medical, 370-378 psychic, 366-370 preparation of patient for colonic ether anesthesia, 450 for oil-ether colonic anesthesia, 460, 461 for spinal analgesia,. 612-613 Preservatives in ready-made anesthesia solutions, 540 Pressure, estimation of, in colonic ab- sorption of ether, 440 in anesthetization of skin, 493 in local anesthesia, 477 regulation of, in colonic ether anes- thesia, 443 Pressure anesthesia, 552 Priestley, discovery of nitrons oxid by, 118 discovery of oxygen by, 893 Prinz, Hermann, on local anesthesia as applied in dentistry, 335-553 Proctoclysis in anesthesia, 375 Propasin. See Propesin Propesin, 803 Propion, 689, 804 Propione, 804 Propyl in chloroform, 285 Propyl alcohol, impurities in ethyl chlorid due to, 253 Propyl ester of dimethyl-amino-oxy- benzoyl-isobutyric acid, 820 Propylene, 689 Prostatectomy under local anesthesia, 513 under spinal analgesia. Young 's op- eration for, 592 Proteid compound theory of anesthesia, 44, 45 Protoplasm, physicochemieal constitu- tion of, 52 Protoplasmic respiration and anes- thesia, 42, 43 Pseudotropin-liebermann, 832, 833 Psoas sinus enlargement in child under spinal analgesia, Lusk's case of, 584, 585 Psychic influences and surgical anes- thesia, 650, 651 Psychic shock, 384-387 Psychic treatment preliminary to anes- thesia, 366-370 Puerperal eclampsia, anesthetic treat- ment for, 667 Puerperal sepsis, sequestration anes- thesia contra-indicated in, 470 Puff-ball, 804 Pulmonary anesthetics, preliminary use of morphin in, 370, 371 Pulmonary complications after ether, Otte on, 199 Pulmonary method preliminary to colo- nic method, 451 Pulmonary tuberculosis, chloroform in- dicated for, 310. See also Phthisis INDEX 935 Pulp, dental, method of anestlietizhig, 552, 553 Pulpitis, use of ethyl chlorid contra-in- dicated in, 538 Pulse and shock, 383, 410-413 in anesthol anesthesia, 277 in chloroform anesthesia, 307-309, 316 in ethyl chlorid anesthesia, 274 in ethyl-chlorid-oxygen anesthesia, 278 in intratracheal anesthesia, 429 in nitrous oxid anesthesia, 133 in oil-ether colonic anesthesia, 462, 463 in operations under anoci-association, 405, 406 in spinal analgesia, 582 Pulselessness in overdose of ethyl chlorid, 261 Puncture site, cotton and collodion dressing on, 622, 623 location of, in spinal analgesia, 620 painted with iodin in spinal anal- gesia, 618 Pupillometer, 195, 308 Pupils in chloroform administration, 306, 308, 315 in colonic ether administration, 453 in ethyl chlorid anesthesia, 262 Pyemia, spinal analgesia contra-indi- cated in, 587 Pyknometer for determining specific gravity of chloroform, 889 for determining specific gravity of ether, 864, 865 Pylorectomy under spinal analgesia, 560 Pyridin, 804 Pyroacetic ether, 689. See also Ace- tone Pyrocain, 804 * ' Pyrogenous ' ' oil in chloroform, 285 Pyrollidin, 804 Pyrrol, 714, 804, 805 Quincke 's experiments with lumbar puncture, 557, 559, 563 Quinin, 540 and urea hydrochlorid, 805 in anesthetic block for shock preven- tion, 406 in gastro-enterostomy, 356 solutions of, in local anesthesia, 478 Quinin alkaloids, 805 Eadestock 's mixture, 807 Eadikal-anasthetikum apotheker Maier, 807 Eadinin, 807 Eamsay, on decomposition of chloro- form, 885 Eape, anesthesia and, 687 Eapid respiration, anesthesia by, 807 Eathery on effects of ether on kidneys and liver, 190 Kaueher on effect of ether on lactation, 192 Kebrcathing, advantages of, 113 charts showing effect of, on pulse, respiration, and blood pressure, 105, 106, 107 in administration of anesthetics, 99- 116 in chloroform administration, 317 in chloroform-ether-nitrous oxid se- quence, 141, 142 in colonic ether anesthesia, 451, 452 in nitrous oxid anesthesia, 137, 140, 141, 142 in nitrous oxid-oxygen anesthesia, 129, 144, 145, 159, 166, 167 in oil-ether colonic anesthesia, 462 in shock cases, 112 Eeclus, 478, 489, 539, 753 Eectal anesthesia, 225 by colonic absorption of ether, 433- 458 in diseases of the lungs, 330 preliminary use of morphin in, 370 statistics for, 843, 855 Eectal cases, anesthesia in, 355 Eectal diseases, cyclorenal in, 732 Eectal ether, statistics for, 842 Eectal infusion in shock prevention, 404 Eectal tube in colonic ether anesthesia, 443, 449, 451, 461, 463 Eectification of ethyl chlorid, 253 Eectum, sagittal section of, 517 surgery of, under local anesthesia, 514, 515, 516, 517 under spinal analgesia, 587 Eedistillation of ethyl chlorid, 253 Eedwood, on action of sulphuric acid on chloroform, 878 Eeflex, lid, in oil-ether colonic anesthe- sia, 462 Eeflexes, after anesthesia, 378 cutaneous, and surgical shock, 383 in chloroform anesthesia, 307, 308, 315, 316 in ethyl chlorid anesthesia, 260, 262, 263 in nitrous oxid anesthesia, 133 Eegional method of local anesthesia, 490 Eegionary anesthesia, eueain lactate anesthesia for, 758 Eegnault, formation of carbonyl chlorid in chloroform demon- strated by, 884 on chloroform, 873 Eeicher's theory of anesthesia, 47, 48 Eeichel's zahnschmerzstillende Tropfen, 807 Eemoval of patient after operation, technique of, 377 Eenal function, effect of anesthesia on, 60 Eenocain, 808 Eenoform, 808 Eesistanee to surgical shock, 383, 384 936 INDEX Respiration and shock, 383, 385, 410- 413 during oil-ether colonic anesthesia, 462, 463 e&eet of warming the agent on, 65 in anesthesia, 57 in anesthol anesthesia, 277 in chloroforin administration, 287, 288, 298, 313, 316 in ethyl chlorid anesthesia, 258, 263, 274 in ethyl chlorid-oxygen anesthesia, 278 in nitrous oxid anesthesia, 127, 133 in sequestration anesthesia, 469, 472 in stage of overdose of nitrous oxid, 134 rapid, aiiesthesia by, 807 Eespiratory conditions under spinal analgesia, 582 Eespiratory difficulties during anesthe- sia, 380, 381 Eespiratory failure due to loss of car- bon dioxid in blood, 406-408 Eespiratory system, anesthesia in op- erations on, 339 effect of anesthetics on, 56, 57 effect of ether upon, 185, 192, 248 effect of ethyl chlorid on, 258, 259, 269 effect of nitrous oxid on, 127, 128 reflex changes in, in anesthesia, 62 See also Lungs Eetching during anesthesia, 381 Eey, Jean, 893 Eeyne's anesthetic mixture, 689, 702 Eeynier, on nirvanin, 781, 782 Rhein, methyl chlorid as a refrigerat- ing agent introduced by, 537 Ehigolene, 808 Ehinolaryngology, novocain in, 784 Ehinosol, 808 Eib resection for empyema under local anesthesia, 505 Richardson, methyl alcohol introduced by, 773, 774 methyl bromid introduced by, 774 methyl chlorid introduced by, 775 methyl ether introduced by, 776 methylal introduced by, 776, 777 methylene chlorid introduced by, 777 methylene ether introduced by, methylic-ethylic ether proposed 778 on amyl nitrite, 698 on amylene, 698 on butyl chlorid, 718 on carbon dioxid, 719 on carbon disulphid, 720 on ethyl bromid, 738 on ethylene ■ chlorid, 749 on hydramyle, 767 on local anesthesia, 477 on methane, 773 on puff ball, 804 778 by, Eichardson, on turpentine, 837 statistics of, for ether and for chloroform, 853 Eichardson 's methylen chlorid, 808 Eichardson 's mixture, 689, 808 Eichardson 's voltaic narcotism, 536 Eigidity, muscular, during anesthesia, 381 induced by hypnosis, 659, 660, 663 Eingen's solution in intravenous anes- thesia, 525, 532 with carbon dioxid in prevention of shock, 409 Ritsert's anesthesin, 702 Eoaf theory of anesthesia, 44-46 Eobinovitch, Louise G., on electric analgesia, sleep, and resuscita- tion, 628-643 Eobiol, 808 Eohricht on glycosuria after ether, 198 Eolland, somnoform introduced by, 818 Eose, Valentin, on ether, 860, 863 Eoth-Drager oxygen and chloroform apparatus, 317-320 Eottenstein, on ethyl chlorid as a re- frigerating agent, 537 Eoux, on decomposition of chloroform, 884 on spinal analgesia, 604 Rouxeau, physiological investigations of, on electric sleep, 629 Eouxeau and Leduc, experiments of, on electric anesthesia, 628 on electric resuscitation, 637 Eoyal Medical and Chirurgical Society Committee mixture, 808 Eump, on effect of air and light on chloroform, 884 Eyall on spinal analgesia, 587, 604, 610 Eyan and Guthrie on magnesium salts, 771 Eymer and nitrous oxid, 24 Safrol as preservative of chloroform, 292 Sahli, pantopon introduced by, 798, 799 Saison on effects of ether on the liver and kidneys, 190 Sal angestheticum Schleichii, 808, 809 Salicylchloroform, 877 Saline enema during anesthesia, 374, 375, 376 in acid intoxication, 414 in post-operative treatment, 378, 379 in preliminai'y medication, 373 in treatment of shock, '374 Saline infusion in shock prevention, 403, 404, 409 intravenous administration of, in oil- ether colonic anesthesia, 462, 463 intravenous infusion of, effect of, on blood pressure, 403 normal physiologic, as vehicle for analgesic drugs in local anesthe- sia, 479 INDEX 937 Saline, use of, following adenoid and tonsil operations, 345 in acute mania, 669 in eocain solutions, 480, 481 in eocain sterilization, 605 in intravenous anesthesia, 525 in spinal analgesic solutions, 599, 603 Saline solution and glucose, use of, pre- ceding anesthesia in cancer, 330 Saline solution infiltration in local an- esthesia, 489 Saline solution injection into sub- arachnoid space, 557 Salivary glands, effect of anesthesia on, 60 effect of warming the anesthetic on, 70 Salolcamphor, 809 Salolum camphoratum, 809 Salpingectomy under spinal analgesia, 560 Salts, antagonism between anesthetics and, 55 Salts of arabic acid with anesthetic bases, 713 Salvarsan method of introducing needle in intravenous anesthesia, 528 Sander's chloroform vapor generator in colonic ether apparatus, 444 Sanoform preparations, 809 Sanovagin, 727. See also Coeainol- ereme Sansom's A. C. mixture, 809, 810 Saponin with chloroform, 284 Scalp, anesthetization of, 496, 497 eocain solution for local, 497 nerve supply of, 497 Scar removal under local anesthesia, 495 Sehacht on Pictet chloroform, 877, 880, 881 Schafer and Scharlieb's A. C. mixture, 810 Schall on oxygen and chloroform, 27 Scheele, oxygen prepared by, 893 Schering's method of preparing chloro- form, 873 Schleich's anesthetics, 810 Schleieh's experiments with anesthetic mixtures, 702-705 Schleich's infiltration anesthesia, 755 acoin in, 690 alypin in, 693 in spinal analgesia, 559 use of tropacocain hydrochlorid in, 833 Schleich's method of anesthesia, 484, 489, 808, 809 Schleich's solution No. 2, statistics for, 842 Schleich's theory of anesthesia, 35, 36 Sehmitt on eueain-B, 754 Schneiderlin-Korff method of anesthesia by morphia and scopolamin, 811 Schoorl and Van den Berg, on decom- position of chloroform, 887 Schraff' 's discovery of local analgesia with coeain, 555 Sciatica, eucain-B in treatment of, 755 Sclerosis of arteries, nitrous oxid anes- thesia contra-indicated in, 135 Scopolamin, in goiter, 354 in intravenous anesthesia, 524, 533 in preliminary medication, doses for, 372 for colonic ether anesthesia, 450, 454 for nitrous-oxid-oxygen anesthesia, 165 Scopolamin hydrobromid, 810-817 Scopolamin-morphin injection in local anesthesia, 486 Scopolamin-morphin-ether anesthesia, 813 Scopolamin-morphin-ether chloroform anesthesia, 814 Scopolamin tablets, 813 Scopomorphin, 817 S-dichlorethane, 749, 750 Sealed tube of ethyl ehlorid, 254 Seasickness, antivom in, 712 Sebaceous cyst removal under local an- esthesia, 495, 496 Seelig on ether inhalation, 198 Selection of anesthetic, conditions af- fecting, 324-326 for special operations, 337-357 rules to be observed in, 326-337 Semi-closed method of administering ethyl ehlorid, 272, 273 Sensory innervation of mucous mem- branes of head, 499 Sensory nerves, eocain experimentation on, 556 Sensory paralysis in venous anesthesia, 492 Sepsis, spinal analgesia contra-indi- cated in, 587 Septicylat, 817 Sequestration method of anesthesia, ad- vantages of, 470-473 contra-indieations to, 469, 470 disadvantages of, 473 history of, 467, 468 indications for, 469 modifications in method of, 470 technique of, 468, 469, 471, 472 with upright position, 473-475 Shock, anesthetic, 387-401 anticipation of, 410-413 causes of, 401, 405 dietetic, 387 diminution of, in upright position for adenoid and tonsil operations, 352 due to obstructed airway, 389 due to overdose of anesthetic. 388 duration of operation and, 386 during anesthesia, 374, 389 effect of hemorrhage on, 387 93S INDEX Shock, effect of, on cerebrospinal fluid, 565 effect of pituitary extract on, 404 effect of posture on,- 402, 404 effect of preliminary medication on, 371 from labial stertor, 390 in operation. on appendix, 413 in spinal analgesia, 581, 587, 595 intravenous infusion and, 404 physiologic rest in treatment of, 404 post-operative, adrenalin in preven- tion of, 373 prevention of, 376, 379, 382-413 by Crile, 402-406 by support of circulation, 404 Henderson on, 409 in local anesthesia, 485 Keen 's measures for, 404 measures for, by Latham and Eng- lish, 403 saline infusions in, 404 water in, 366 psychic, 384-387 reduction of, in colonic ether anes- thesia, 457 surgical, 383, 384 and time of day, 384 susceptibility of organs to, 402, 403 theories of cause of, 401 Crile 's vasomotor paralysis, 402- 406 Henderson 's vasomotor activity, 406 treatment of, 392-401, 666 treatment of, in accordance with Crile 's theory, 403-406 Shoulder amputation imder local anes- thesia, 490 Shuttle^sorth 's method of purifying chloroform, 879 Sicard on spinal analgesia, 558, 566 Sicard's experiments on injections into •subarachnoid space, 557, 558 Sicherheitsbenzih, 817 Silliman, chloroform confused with ethylen dichlorid by, 871 on production of chloroform, 872 Silver nitrate in testing purity of oxy- gen, 895 Simpson, Sir James Y., 8, 20, 21, 22, 25, 177, 282, 286, 311, 689, 713, 720, 749 Simpson 's ' ' Anaesthesia, ' ' 21 Simpson's "New Anaesthetic," 20, 21 Sims' position in oil-ether colonic anes- thesia, 461, 465 Sinecain, 817, 818 Skin, appearance of, in nitrous oxid anesthesia, 133 local anesthetization of, 493-496 production of wheal in, 493-495 solution for, 494 Skin affections, ethyl aminobenzoate in, 737 Skin and surgical shock, 383 Skin grafting under colonic ether an- esthesia, 454 under local anesthesia, 511 Skin injection, solution for, in local anesthesia, 480 Skin reflexes due to shock, 385 Skopomorphin. See Scopomorphin Sleep, 51 difference between anesthesia and, 50 Sleeping child, method of anesthetiz- ing, 341, 342 Skull examination under local anesthe- sia, 496 Skull fracture, operation for, under colonic ether anesthesia, 456 Smokers, ethyl chlorid anesthesia con- tra-indicated in, 269 Snape 's ' ' calorific fluid, " 536 • Sneezing during anesthesia, cocain for, 381 Snow, John, 25, 177, 283, 713, 719, 720, 749 Snow's inhaler, 23 Soapsuds enema after oil-ether colonic anesthesia, 463 in after-treatment for colonic ether anesthesia, 453 in preliminary treatment, 375 for colonic ether anesthesia, 450 Sobbing in anesthesia, 380 Sodium bromid in post-operative vom- iting, 379 Sodium carbonate in preparation of chloroform, 879 in purification of chloroform, 285 Sodium chlorid, in preparation of co- cain solutions, 539 in preparation of ethyl chlorid, 252 in spinal analgesic solution, 601, 602 with cocain in local anesthesia, 480, 482 Sodium hydroxid as preservative of chloroform, 291 in testing purity of oxygen, 895 Sodium nitrite, 401 Sodium nitroprussid solution in test- ing chloroform, 890 Sodium thiosulphate, in purification of chloroform, 879 Scemnoforme. See Somnoform. Soloid "hemisine" comp. c. eucaino, 818 Solubility of chloroform, 284 Soluble hypodermic tablets novocain % grain, 818 Soluble tablets novocain 1 1/7 grains, 818 Solution atoxyl, 10 per cent., with novocain, 1 per cent., 818 Somnambulism, hypnotic, 654 Somnoform, 276, 818, 819 and local anesthesia, 856 effect of, on diaphragm, 258 statistics for, 856 INDEX 939 Somnoform-cliloroform, statistics for, 856 Somnoi or m-other-clilorof orm, statistics for, 856 Somnolence, hypnotic, 654 Soubeiran, discovery of chloroform by, 871, 873 Souligoux on ether in the treatment of infections, 671, 672 Spasm, muscular, in asphyxia, with ethyl chlorid, 261 Spasms, muscular, due to chloroform, 303 Specialist, liability of, 684, 685 Speier's ansesthin and anaesthol solu- tion, 702 Spencer's theory of anesthesia, 32-34 Spermaceti, purified, as preservative of chloroform, 292 Sphincter ani, dilatation of, 463 in treatment of shock, 393 Spielmeyer's experiments in spinal analgesia, 570, 571 Spiller and Leopold's experiments, with stovain in spinal analgesia, 569, 570 Spilsbury and Cross, on purity of chloroform, 882 Spinal analgesia, 554-627 advantages and disadvantages of, 594-596 alypin in, 693 analgesic agents for, 599-604 sterilization of, 604, 605 anatomical and physiological consid- erations' in, 563-572 apparatus and materials for, 614-616, 617 sterilization of, 616, 617 auto-operations under, 577, 580 Babcock's solution for', 603 Barker 's stovain-glucose solution for, 602, 603 Bier's stovain solution for, 602 Bier's tropacocain solution for, 601 Braun 's novocain-suprarenalin solu- tion for, 603, 604 by tropacocain, 601, 835, 836, 837 case reports on, 623-627 cases of complete, 574, 575, 576 in children, 588-590 Chaput 's stovain solution for, 602 course of, 572 deaths due to, 596-598 decrease of post-operative pneu- monias imder, 199 discovery of, 555-563 duration of, 576, 577 early application of, to surgery, 559- 563 Erhardt's solution for, 601 extent of, 572-576 facial expression of patient under, 575 first surgical operation under, 559, 560 Spinal analgesia, Gray's dextrin-stovain solution for, 603 history of, 555-563 in diseases of the lungs, 330 in heart disease, 329 in obstetrics, 593, 594 indications and contra- indications for, 586-594 opinions of surgeons on, 586, 587 injection with patient in recumbent position, 614 Jonnesco's stovain-strychnin solu- tion for, 603 Meyer's solution for, 601 operations on the aged under, 591, 592 phenomena accompanying, 577-582 objective, 581, 582 subjective, 577-581 postoperative phenomena of, 582- 586, 595, 596 preliminary use of morphin in, 370 preparation of patient for, 612-614 scopolarnin sleep combined with, 813 sites of injection in, 564, 605-612 statistics for, 842, 843, 855 technique of injection in, 595, 617- 623 typical satisfactory case of, 625 Spinal cord, cocain experimentation on, 556-559 illustrations of, 608-610 lesions of, spinal analgesia contra- indicated in, 587 Spinal neurons, effects of anesthesia on, 41 Spinal puncture, early experiments in, 557, 558 Lusk on, 605-607 patient in sitting posture for, 613 routes for, 605, 607-610 Eyall's method of, 610 schematic pictures showing location of space between third and fourth lumbar vertebrse, 611 Spinal puncture site, location of, 618 Avamreseo 's, 610 Gray's, 610 Jonnesco 's, 607, 608 painted with iodin, 618 Spinal support during local anesthe- sia, 486, 487 Spine, diagrammatic cross-sections through, 606 Spleen, enlargement of, in status lymphaticus, 332 Spraying nozzle for ethyl chlorid, 254 Squibb on manufacture of ether, 860 Staphylorrhaphy under colonic ether anesthesia, 439, 454, 456 under rectal etherization, 435 Starfish eggs, effect of anesthetics on, 43, 44 Starvation, acidosis in, 415 Starvation cases, gastroenterostomy in, 356 940 INDEX Statistics, 841-857 American, 843 for 1905-1912, 854-856 comparison of American and Euro- pean, 853, 854 comparison of 1905-11, with 1892, 853 for anesthol, 848 for auesthol-ether sequence, 847 for chloroform,' 851, 852 for chloroform-ether sequence, 847 for chloroform-oxygen, 851 for ether, 848 for ethyl chlorid, 848-850 for ethyl chlorid-ether, 848 for intratracheal anesthesia, 852 for local anesthesia, 844 for nitrous oxid, 844 for nitrous oxid with oxygen, 844- 847 for nitrous oxid-ether sequence, 848 for oil of bitter orange peel-ether sequence, 852 U. S. army, 842, 852 U. S. navy, 842, 852 See also under various anesthetics Status lymphaticus, 326, 327 anatomy of, 331, 332 chloroform contra-indicated in, 310 choice of anesthetic in suspected cases of, 333 definition of, 331 diagnosis of, 332, 333 ether for, 247 history of, 331 mortality from, 334, 335 observations on, in animals, 335-337 post-mortem examination in, 335 preparation for operation in, 333, 334 treatment of, during anesthesia, 334 Statutory liability of physician, 686, 687 Stenocarpin, 819 Stephan's analgos, 710 Stephen's mixture, 819 Sterilization of analgesic agents, 604, 605 of apparatus for spinal analgesia, 616, 617 Sterno-mastoid excision under colonic ether anesthesia, 454 Stertor in anesthesia, 380, 464, 465 in chloroform administration, 307 in ethyl chlorid anesthesia, 274 in oil-ether colonic anesthesia, 462 labial, shock from, 390 prevention of, during anesthesia, 392 Stimulation, peripheral, during anes- thesia, 380, 381 Stitch irritation, prevention of, by an- esthetic block, 406 Stockman and nitrous oxid, 5 Stomach, care of, preliminary to local anesthesia, 486 Stomach operations, shock in, 403 Storage of ethyl chlorid, 254-256 Stovain, 540, 692, 819-828 in spinal analgesia, 563, 576, 582, 599, 603, 624, 625, 626 with adrenalin, 592 with strychnin, 828, 829 Stovain injection by lumbar puncture, effect of, on nervous system, 569, 570, 571, 572 Stovain solutions in spinal analgesia, 602, 603 diffusible, 585 Stovain-Billon, 828 in spinal analgesia, 602, 603 Stovain- dextrin solution in spinal anal- gesia, 592 Stovain-glucose solution in spinal anal- gesia, 602, 603 Stovain-strychnin solution in spinal analgesia, 582 Strophanthin, 829 Strychnin, stovain with, 828, 829 use of, in respiratory disturbances, 539 in respiratory failure, 394 in spinal analgesia, 563, 582, 585, 599, 603, 604, 612 Strychnin injection in shock preven- tion, 403 Strychnin poisoning, anesthetic treat- ment for, 667 chloroform in, 285 Strychnin sulphate in shock preven- tion, 403 in spinal analgesia, 625 Sturmann 's solution, 829 Stursberg, on effects of ethej narcosis on the blood, 188 on temperature stimulus in ether and chloroform anesthesia, 69 Subcain, 829 Subcutin, 829, 830 Subcutol, 829 Subicterus, post-operative, following sequestration anesthesia, 472 Submucous operations, anesthesia in, 340 Subperiosteal injection of anesthetic solutions in dentistry, 543-547 Suffocation, due to enlarged thymus, 335 Suggestibility in hypnosis, 654 factors influencing, 655, 656 Suggestion in anesthesia, 649-653 deep breathing and, 652, 653 instead of hypnotism, 649, 650 local anesthesia and, 651, 652 preliminary medication and, 653 value of, 652 See also Hypnosis Sulphate of morphin, use of, preceding anesthesia, 328 Sulphates, preparation of oxygen from, 894 Sulphocarbolate. See Subcutin INDEX 941 Sulphophenalylate. See Subcutin Sulphur, as preservative of chloroform, 291, 292 in preparation of chloroform, 875 Sulphur compounds, test for, in ethyl chlorid, 257 Sulphur dioxid, removal of, from ether, 864 Sulphuric acid in chloroform, 285 in preparation of ether, 180, 860, 862 in preparation of ethyl chlorid, 252, 253 in purification of chloroform, 878, 879, 890 preparation of oxygen from, 894 Sulphuric ether, 178, 860 Sulzberger 's local ana3sthetic, 830 Summopon, 830 Superior maxilla operations under co- lonic ether anesthesia, 454 Suppositoires adreno-styptiques, 830 Suprarenalin in spinal analgesic solu- tions, 603, 604 Suprarenal-tonogen, 830 Suprarenin, 830 synthetic, 692 Suprarenin-cocain tablets. See Braun 's Suprarenin tablets Surface anesthesia, 488, 489 Surface tension theory of anesthesia, 42 Sutton's apparatus for colonic absorp- tion of ether, 437, 438, 439 description of, 444-450 afferent and efferent tube systems, 449, 450 complete with oxygen tank, 448 simple form of, 447 vapor generator, 444-449 Sutton's method of ether adminis- tration by colonic absorption, 441 administration in, 451-453 after-treatment, 453 preparation of patient for, 450 technique of, 450-453 Sweat glands, effect of anesthesia on, 60 Sweating in spinal analgesia, 582 "Sweet spirit of salt," 250. See also Ethyl chlorid Sylvester, use of quinin and urea hy- drochlorid by, 806 Synthetic suprarenin with novocain in local anesthesia, 482 Syringe for Bier 's venous anesthesia, 491 for injections in local anesthesia, 483, 484 for spinal analgesia, 614 Tait on spinal analgesia, 560, 561, 562, 565, 566, 607 Tait and Caglieri's experiments on the subarachnoid space, 565-572 Tauber, experiments of, with trichlor- ethane, 832 studies of, on methylchloroform, 832 Teeple, on preparation of chloroform from acetone, 874 Teeth, cocain anesthesia of, 489 operations on, under local anesthe- sia, 496 See also Dentistry Temperature (body), effect of amyl chlorid on, 697 effect of anesthesia on, 66, 67 effect of warming the agent on, 67- 69 in colonic ether anesthesia, 436, 4-52 in oil-ether colonic anesthesia, 462 in operations under anoci-associa- tion, 405, 406 rise of, due to chloroform and ether mixture, 706-710 shock and, 383, 38.5, 386, 402 Tendon transplantation under local anesthesia, 511 Tenesmus in colonic ether anesthesia, 435 ' ' Terminal anesthesia, ' ' 536 Terpentinkampfer. See Terpin hydro- chlorid Terpentinchlorhydrate. See Terpin hy- drochlorid Terpin hydrochlorid, 831 Terpinchlorhydrate, 831 Terpineol as preservative of chloro- form, 292 use of, preceding anesthesia, 91 Testicles, effect of shock on, 385 Tetanus, anesthetic treatment for, 667 chloroform indicated for, 310 Tetanus toxin injection into subarach- noid space, 558 Teter auxiliary tube, 155, 173 Teter ether attachment, 154 Teter face mask, 154 Teter method of nitrous oxid-oxygen anesthesia, 153-159 Teter nasal inhaler, 155, 156 Teter nasopharyngeal tubes for nitrous oxid and oxygen, 157 Teter nitrous oxid-oxygen apparatus, 152, 156 Teter vapor warmer, 153 Teter 's case of death in nitrous oxid and oxygen anesthesia, 845, 846 Tetrachlorethane, 831 Tetrachlorethylene in chloroform, 285 Tetrahydronaphthalene, 831 Tetramethyl - diamino - dimethylethyl- carbinol cinnamate hydrochlorid, 831 Thayer's method of purifying chloro- form, 879 Thibault, use of quinin and urea hydro- chlorid by, 483, 806 Thibault 's local anaesthetic, 831 Thin subjects, choice of anesthetic for, 329 942 INDEX Thirst, relief of, during anesthesia, 374, 375 Thomas' apparatus for colonic ether anesthesia, 437, 444 for pharyngeal anesthesia, 437 Thompson on effects of ether upon renal activity, 190, 191 Thoracic surgery, intratracheal insuf- flation indicated in, 431 under local anesthesia, 505, 506 under spinal analgesia, 597 Three-bottle vapor inhaler, 225, 230 attached to oxygen tank, 240 Throat affections, dysphagin in treat- ment of, 735 Throat operations, alypin in, 693 eucain lactate solution for, 758 with Sutton's colonic anesthesia ap- paratus, 450 Thrombosis after ether, 186, 199 Throphene, 714 Thymicus, 331-337. See also Status lymphaticus Thymocain, 831 Thymoform, 831 Thymol, 692 as preservative of chloroform, 292 in carbon tetrachlorid for steriliza- tion in intravenous anesthesia, 526, 531 Thymus gland, 331, 332 enlargement of, 333, 335 See also Status lymphaticus Thyroglossal cyst operations under colonic ether anesthesia, 454 Thyroid, enlargement of, in status lymphaticus, 332 operations on, methods of, 503-505 sequestration anesthesia in, 471 under local anesthesia, 502-505 See also Thyroidectomy Thyroid arteries, ligation of, under local anesthesia, 502, 503 Thyroidectomy, anesthesia in, 353 cocain solutions in, under local an- esthesia, 480 intratracheal insufflation in, 432 sequestration anesthesia indicated in, 469 under anoci-association, 406 under local cocain anesthesia, 581 Tibia, osteotomy of, under spinal anal- gesia, 560 Tilden, on action of sulphuric acid on chloroform, 878 Tin containers for chloroform, 293 Tissue asphyxia, 124 Toe anesthetization, 507, 511 Toes, operations on, 354 Esmarch elastic bandage in, 477 Tongue, enlargement of, in status lymphaticus, 332 excision of, anesthesia in, 339, 340 chloroform indicated for, 310 under colonic ether anesthesia, 435, 454, 455 Tongue, excision of, under local anes- thesia, 497, 498 under oil-ether colonic anesthesia, 464 under spinal analgesia, 587 Tongue forceps, use of, in anesthesia, 362 in artificial respiration, 393 Tonocainum suprarenale Eichter, 831 Tonogen suprarenale Eichter, 831 Tonsil cases, 340-352 use of ether for, 247 use of Junker apparatus in, 322 See also Adenoid and tonsil cases Tonsillectomy, ethyl chlorid anesthesia for, 268 local anesthesia for, 500 sequestration anesthesia for, 470, 474 Tonsils, enlargement of, in status lymphaticus, 332 treatment of, under local anesthesia, 499, 500 Torney, Surgeon-General, 891 Townley 's anodyne mixture, 831 Toxemia, induced by thymus, 335 post-anesthetic, 413 use of water during anesthesia in, 376 Toxic causes of psychic shock, 384 Trachea, operations around, intra- tracheal insufflation indicated in, 432 operations on, colonic ether indicated in, 457 Tracheotomy, anesthesia in, 352, 353 under colonic ether anesthesia, 454, 455, 456 under local anesthesia, 502 Transfusion of blood in serious cases of shock, 404 preceding gastro-enterostomy, 356 Traube 's theory of anesthesia, 42 Traumatic surgery, intravenous anes- thesia in, 492 Treatment after anesthesia, 378, 379 by colonic absorption of ether, 453 local, 488 anesthetic, for special conditions, 666-671 emergency, to insure breathing, 362, 363 for acapnia, 409 of ordinary cases during anesthesia, 364-379. See also Management of unusual cases, 379-415. See also Management preliminary, in ordinary cases, 364- 374 Tremors, muscular, during anesthesia, 381 Tri-bromo-methane. See Bromoform Trichlorbutylidene glycol. See Butyl- chloral hydrate Trichlorethane, 831, 832 INDEX 943 Trichlorethylen dichlorid. Sec vEther auajstheticus aranii Trichlorisopropylalcohol, 768 Trichlormethane, 281. See also Chloroform Trichlorurum formili. See Chloro- form Trimethylbenzoxypiperidinum hydro- chloricum. See Eucain-B. Trimethylethylen, 698, 801, 802, 832. Sec also Amylene Trismus during anesthesia, 381 Tropacocain, 540, 754, 832 in spinal analgesia, 563, 571, 576, 583, 599, 600, 601, 604 Tropacocain hydrochlorid, 832, 833 Tropein, 832. See also Tropacocain Tube systems, afferent and efferent, in Sutton's apparatus for colonic anesthesia, 449-451 Tubes for ethyl chlorid, 254-256 glass nasal, for general anesthesia, 227 Tuberculosis, choice of anesthetic in, 329 use of guaiasanol in, 762, 763 Tucker, use of magnesium sulphate by, 771 Tufl&er's use of spinal analgesia, 560, 561, 569, 575, 598, 602, 604 Tumor, benign, removal of, under local anesthesia, 485 circumscribed, operation for, under local anesthesia, 489 in airway, chloroform indicated for, 310 in the antromaxillare, case of re- moval of, under hypnotism, 646 of abdominal wall, operation for, under spinal analgesia, 573 of neck, operations on, under colonic ether anesthesia, 454 removal of, by blunt dissection un- der local anesthesia, 496 under the sternum in status lym- phaticus, 332 Turpentine, 837,. 838 oil of, as preservative of chloroform, 292 Typhoid fever, sequestration anesthe- sia contra-indicated following, 470 Udrenin, 838 Ulceration, ethyl aminobenzoate in cases of, 737 Ulcers of tongue, sequestration anes- thesia for removal of, 471 Unipolar methods in inducing electric anesthesia, 631, 632, 636 U. S. Army statistics, 1904-1910, 842 for chloroform, 852 U. S. Navy statistics, 1908-1910, 842 for chloroform, 852 United States Pharmocopo3ia, ethyl chlorid tests prescribed by, 257 Universal anesthotic, 839 Upright position for adenoid and ton- sil operations, 345-352 sequestration anesthesia with, 473- 475 Urea and quinin hydrochlorid in local anesthesia, 483 Urea hydrochlorid, 540 in anesthetic block for sliock pre- vention, 406 in gastro-enterostomy, 356 See also Quinin and urea hydro- chlorid Urea-quinin solution, 722 Urethane, 838 Urethra, anesthetization of, by alypin- gleitmittel, 696 solution for local anesthesia of, 512 Urethritis, ethyl aminobenzoate in, 737 Urethrotomy, external, under local anesthesia, 485 infiltration in, 512 Urinary examination in intravenous anesthesia, 534 Urine, effect of anesthesia on, 60, 61 effect of chloroform upon, 191, 303, 304, 309 effect of ether upon, 190, 191, 197 effect of nitrous oxid on, 132 extravasation of, spinal analgesia in, 587 negative findings in, after ethyl chlorid anesthesia, 264, 265 Urobilinuria following anesthesia, 58 Urosemin, 838 Uterus, effect of shock on, 385 operations on, shock in, 403 Vagina, effect of shock on, 386 Valentine, Basil, 858 discovery of ethyl chlorid by, 250 Valerene. See Amylene Valverdi, 4 Valvular disease, nitrous oxid contra- indicated in, 135 Vanadium steel cylinders for nitrous oxid, 120 Van den Berg and Sehoorl, on decom- position of chloroform, 887 Vanillin, 688 Vanodrin, 839 Vapor, strength of, effect of, on breathing, 380 Vapor anesthesia by open method, 231- 235 Vapor generator in Sutton's colonic anesthesia apparatus, 444-449 Vapor inhaler, first, 24 Vapor mask, 224, 232 Varicose ulcers of legs, operation on, under spinal analgesia, 625 Varicose vein excision under intrave- nous anesthesia, 511 under spinal analgesia, 573, 574 Vascular system, effect of ethyl chlorid on, 258, 260 944 INDEX Vasomotor depression, 316 Vasomotor paralysis as cause of siiock, 402-406 Vein exposed and ligated distally for intravenous anesthesia, 526 Venous, anesthesia, Bier 's method of, 490-492 Ventilation, pulmonary, after ether or chloroform, 107 effect of morphin on, 108 Verliac's apparatus for colonic ether anesthesia, 442 Verrier on effect of ether on lactation, 192 Vertigo following ethyl chlorid anes- thesia, 264 Verworn 's theory of anesthesia, 49, 50 Veterinary surgery, chloral hydrate in, 722 Vienna anesthetic, 689, 839 Vienna Elizabeth Hospital mixture. See Wertheim's mixture Vienna General Hospital Mixture, 839, 689 Vienna mixture, 703, 839 Viferral. See Polychloral Vinci on eucain-B, 754 Vinegar fumes, inhalation of, in post- operative vomiting, 379 "Vinegar naphtha," 736 "Vinous ether," 178 Vinyl trichlorid, 750. See Ethylene chlorid Vinyldiacetonalkamin, 839 Vitriolic ether, 860 Vitriol-naphtha, 860 Vogt on spinal analgesia, 565, 571 Vogt's method of inducing hypnosis, 658 Voltaic narcotism, 536 Vomiting, absence of, following intra- tracheal insufflation, 430 following sequestration anesthesia, 471, 472 after anesthol administration, 278 after colonic ether anesthesia, 438, 453, 455, 458, 464 after ethyl chlorid anesthesia, 264, 265 after use of ethyl chlorid and ni- trous oxid, 279 after use of nitrous oxid, 132 during anesthesia, 381 during chloroform anesthesia, 306, 307 in ether anesthesia, 189 in ethyl-chlorid oxygen anesthesia, 278 in peritonitis or intestinal obstruc- tion, 355, 356 in spinal analgesia, 577, 582, 583, 595 post-anesthetic, 102, 379 effect of carbon dioxid on, 99 effect of oil of bitter orange peel on, 94 Vomiting, post-anesthetic, effect of warming the agent on, 70 lessened by rebreathing, 113 post-operative dosage for, 379 prevention of, by preliminary medi- cation, 373 with Roth-Drager oxygen and chloro- form apparatus, 318 Vreeland oscillator, electric current produced by, 635 Wachsmuth 's mixture, 839 Wade and Finneniore, on alcohol pre- pared from ethyl alcohol, 882 Waite's lokaler Schmerztoter, 839 Walsh, James J., on mental influence in anesthesia, 644-653 War surgery, ethyl chlorid anesthesia in, 266 Ware apparatus for administering ethyl chlorid, 273 Ware's method of administering ethyl chlorid, 272, 273 Warmed chloroform, 314, 315 Warmed ether vapor administration, by closed method, 244-245 amount of anesthetic for, 245 care of apparatus for, 245 Warmed ethyl chlorid vapor, 271 Warming anesthetic agent, 63-76 death following, 67, 68 effect of, on after-effects of anes- thesia, 70 on body temperature, 66-69 on convulsions, 65 on heart action, 65 on recovery from anesthetic, 00 on reflexes, 65 on respiration, 65 experiments in, with ether vapor, 70-76 safety to life and, 63-66 Warming nitrous oxid, 136 Warren and ' ' sulphuric ether, ' ' 5 Warrington on chloroform, 25 Wart removal under local anesthesia, 495 Water as a local anesthetic, 839 formation of, on decomposition of chloroform, 885, 887 preparation of oxygen from, 894 presence of, in chloroform, 889 in ether, 869, 870 role of, in anesthetic ether, 867, 868 Water enema during anesthesia, 374, 375, 376 in post-operative treatment, 379 warm, in oil-ether colonic anesthesia, 460 Water infiltration in local anesthesia, 479, 489 "Water logging," prevention of, 375 Water suction apparatus for adenoid and tonsil operations, 343 Water vapor, inspiration of compressed air with, 77-80 INDEX 945 Waugh on spinal analgesia for chil- dren, 589 Webster on ethyl chlorid, 260 Weidig, 779 Weidig's ansesthol, 710. See also Anasstliol. Wells, Horace, 10, 11, 17, 24 use of nitrous oxid iii dentistry by, 118 Welt ana3sthetikum, 839 Werner 's method of purifying chloro- form, 879 Wertheim's mixture, 839, 840 Westron, 831. See Tetrachlorethane Wheal, production of, in skin anes- thetization, 493-495 Whiskey, administration of, preceding anesthesia in alcoholics, 329 in post-operative treatment, 378 in preliminary medication, 371, 373 with saline enema, 378 White on residue of chloroform, 889 ' ' Wiggers ' anesthetic ether, ' ' 748. See also Ethyl chlorid poly- chlorated Wiki, on magnesium sulphate, 771 Willgerodt 's discovery of acetone chloroform, 724 Williams, Probyn, statistics of, on ether and on chloroform, 854 Williamson on methylated ether, 861 Williamson's theory of etherification, 863 Willstatter, tropacocain prepared by, 832 Wilson 's local anesthetic, 840 Winter rose, 764 Wireless circuits, electric analgesia and sleep in, 631-633, 635, 6:;6 Wood, Alexander, hypodermic injec- tion for dental anesthesia intro- duced by, 536 invention of hypodermic syringe hy, 478 Wood's statistics on ethyl chlorid, 848, 849 Woolsey. See Gwathmey-Woolsey Woolsey method of employing oil of orange-ether sequence, 94, 95 Wright's theory of anesthesia, 40, 41, 42 Wyeth on sequestration anesthesia, 471 Xanthates, 720 Yankauer mask for ether, 203, 232 Yohimbin, 840 Yohydrol, 840 Yvon's method of purifying chloro- form, 880 Ziemssen's experiments with lumbar puncture, 557 Zinc chlorid in preparation of ethyl chlorid, 252 presence of, in ether, 864 Zykloiorm, 840 COLUMBIA UNIVERSITY LIBRARIES This book is due on the date indicated below, or at the expiration of a definite period after the date of borrowing, as provided by the rules of the Library or by special ar- rangement with the Librarian in charge. DATE BORROWED DATE DUE DATE BORROWED DATE DUE i KB 1 e 19. r\ ■^ "X" ! ^-L., ' . SEP 1 196 ) i C28(l I40)M100 f\I)l\ G3S- i^iWH U„WW""B»«Sl.s.«